Summary of your 'study carrel' ============================== This is a summary of your Distant Reader 'study carrel'. The Distant Reader harvested & cached your content into a collection/corpus. It then applied sets of natural language processing and text mining against the collection. The results of this process was reduced to a database file -- a 'study carrel'. The study carrel can then be queried, thus bringing light specific characteristics for your collection. These characteristics can help you summarize the collection as well as enumerate things you might want to investigate more closely. This report is a terse narrative report, and when processing is complete you will be linked to a more complete narrative report. Eric Lease Morgan Number of items in the collection; 'How big is my corpus?' ---------------------------------------------------------- 153 Average length of all items measured in words; "More or less, how big is each item?" ------------------------------------------------------------------------------------ 1919 Average readability score of all items (0 = difficult; 100 = easy) ------------------------------------------------------------------ 45 Top 50 statistically significant keywords; "What is my collection about?" ------------------------------------------------------------------------- 147 TNF 63 cell 53 IFN 35 CD8 33 MBL 32 IL-12 28 IL-6 17 LPS 15 patient 15 SARS 14 COVID-19 12 IL-1 11 result 9 study 9 level 9 increase 9 effect 9 disease 8 dna 8 PCR 7 inflammatory 7 expression 7 University 7 ELISA 6 virus 6 sepsis 6 mouse 6 figure 6 RNA 6 Fig 5 treatment 5 response 5 protein 5 high 5 gene 5 TNF- 4 receptor 4 method 4 infection 4 human 4 cytokine 4 control 4 SLE 4 MHC 4 IL-4 4 IL-10 4 CD4 3 western 3 endothelial 3 die Top 50 lemmatized nouns; "What is discussed?" --------------------------------------------- 28846 cell 12188 patient 8081 % 8063 expression 8020 protein 7882 response 7788 level 7740 study 6758 effect 6043 result 6014 cytokine 5581 disease 5522 mouse 5182 group 5140 factor 4977 gene 4889 activity 4850 receptor 4560 infection 4508 role 4262 treatment 4218 blood 4193 activation 4088 production 4086 control 3806 p 3753 t 3671 macrophage 3555 antibody 3282 type 3211 day 3177 method 3170 tissue 3071 analysis 3012 time 2978 concentration 2968 virus 2875 system 2764 molecule 2741 datum 2721 pathway 2573 function 2487 antigen 2479 inflammation 2432 cancer 2422 model 2414 mechanism 2394 lung 2273 serum 2270 conclusion Top 50 proper nouns; "What are the names of persons or places?" -------------------------------------------------------------- 5364 TNF 3785 IFN 3292 al 2873 T 2709 et 2367 . 2198 MBL 2138 IL-6 1930 þ 1600 mg 1599 LPS 1561 C 1539 AE 1381 CD4 1308 IL-10 1286 CD8 1239 α 1217 MS 1204 II 1068 der 1062 University 1033 HLA 1018 IL-12 1015 A 983 NK 965 g 939 SARS 910 PCR 870 a 859 IL-1 847 mRNA 806 RNA 803 B 801 S. 789 kg 770 DC 760 MHC 730 ELISA 693 E. 668 COVID-19 638 CSF 634 M 629 G 567 ¼ 560 Fig 559 NF 538 IL-2 530 ICU 514 M. 513 I Top 50 personal pronouns nouns; "To whom are things referred?" ------------------------------------------------------------- 11225 we 4073 it 1919 i 1321 they 638 them 449 one 182 us 181 itself 138 he 102 iga1 83 she 56 themselves 33 eph-4 26 you 20 me 12 him 7 interleukin-10 6 mrnas 6 her 4 s 4 em 3 interleukin-15 3 igfbp2 3 himself 2 rhil-10 2 itsn2 2 il1-α 2 il-1β 2 il-12 2 igmcic 2 ifnyr-/-mice 2 esat-6 2 e2f2-/-mice 2 crx-527 2 c183 1 ␣ 1 ω-3 1 λr1 1 y€ 1 ykl-40 1 y401 1 wi~ 1 w@ 1 tv/ 1 trpm4 1 tnf~ 1 tnfsf7 1 tnfrt 1 thee 1 ta Top 50 lemmatized verbs; "What do things do?" --------------------------------------------- 91220 be 14418 have 7969 use 7079 induce 6377 increase 5935 show 4099 compare 3584 find 3553 associate 3122 suggest 3011 bind 3003 include 2811 activate 2587 do 2575 demonstrate 2506 involve 2448 reduce 2406 investigate 2397 observe 2304 follow 2303 express 2274 mediate 2251 decrease 2182 determine 2154 indicate 1930 inhibit 1923 perform 1917 result 1911 produce 1894 lead 1883 cause 1879 treat 1832 measure 1775 identify 1770 develop 1724 play 1723 study 1699 stimulate 1676 detect 1671 regulate 1628 base 1554 evaluate 1483 report 1476 relate 1466 occur 1448 require 1429 signal 1401 affect 1395 reveal 1380 obtain Top 50 lemmatized adjectives and adverbs; "How are things described?" --------------------------------------------------------------------- 7669 not 7017 - 5827 high 5200 inflammatory 4989 human 4897 also 3819 immune 3433 low 3267 specific 3172 other 3043 such 3011 significantly 2966 anti 2959 different 2897 well 2836 clinical 2833 however 2475 more 2425 significant 2290 only 2108 important 2069 acute 2025 normal 2006 as 1923 first 1898 severe 1752 most 1736 thus 1728 early 1675 dependent 1674 endothelial 1650 further 1558 healthy 1470 cellular 1465 several 1439 non 1436 viral 1433 present 1376 major 1322 respectively 1317 therefore 1258 negative 1238 positive 1220 similar 1220 large 1200 new 1200 multiple 1173 many 1143 molecular 1139 vascular Top 50 lemmatized superlative adjectives; "How are things described to the extreme?" ------------------------------------------------------------------------- 423 most 301 least 237 high 130 Most 104 good 93 low 76 great 44 large 32 strong 28 early 17 late 11 common 9 small 8 bad 7 young 6 close 5 long 5 clear 4 severe 4 old 4 big 4 Trpv6 3 short 3 new 2 ® 2 postt 2 near 2 fit 2 fast 2 B27 1 ~trointesfimd 1 vRNA 1 tt 1 slow 1 slight 1 simple 1 sick 1 safe 1 rich 1 postsurgery 1 poor 1 palienl 1 p=0.0140 1 nfthe 1 mean:-42 1 lfigh 1 hexose 1 furth 1 few 1 ear{i Top 50 lemmatized superlative adverbs; "How do things do to the extreme?" ------------------------------------------------------------------------ 1329 most 172 least 77 well 4 erv1 2 α2-ar 1 youngest 1 lowest 1 highest 1 fast 1 early 1 -significantly Top 50 Internet domains; "What Webbed places are alluded to in this corpus?" ---------------------------------------------------------------------------- 5 www.genego.com 3 www 2 www.drugbank.ca 2 www.vin.com 1 xcmsonline.scripps.edu 1 www.spss.com 1 www.pharmacases.de 1 www.ncss 1 www.ncbi.nlm.nih.gov 1 www.ncbi.nlm 1 www.mirbase.org 1 www.mdpi.com 1 www.jax.org 1 www.has-sante.fr 1 www.genome.gov 1 www.frontiersin.org 1 www.cwauthors.com 1 www.chictr.org.cn 1 sourceforge.net 1 rstats.immgen.org 1 pubchem.ncbi.nlm.nih.gov 1 ped-rheum 1 orcid.org 1 mml.spbstu.ru 1 dx.doi.org 1 doi.org 1 creat 1 clinicaltrials.gov 1 adz.cf.ac.uk Top 50 URLs; "What is hyperlinked from this corpus?" ---------------------------------------------------- 3 http://www.genego.com/pdf/MC_legend 3 http://www 2 http://www.drugbank.ca/ 2 http://www.VIN.com 1 http://xcmsonline.scripps.edu/ 1 http://www.spss.com 1 http://www.pharmacases.de 1 http://www.ncss 1 http://www.ncbi.nlm.nih.gov/geo/ 1 http://www.ncbi.nlm 1 http://www.mirbase.org/ 1 http://www.mdpi.com/2072-6643/12/3/773/s1: 1 http://www.jax.org/ 1 http://www.has-sante.fr/portail/upload/docs/application/pdf/ 1 http://www.genome.gov/ 1 http://www.genego.com/pdf/MC_legend.pdf 1 http://www.genego.com/pdf/ 1 http://www.frontiersin.org/articles/10.3389/fimmu 1 http://www.cwauthors.com 1 http://www.chictr.org.cn/showprojen.aspx?proj=49889 1 http://sourceforge.net/ 1 http://rstats.immgen.org/Skyline_COVID-19/skyline.html 1 http://pubchem.ncbi.nlm.nih.gov/ 1 http://ped-rheum 1 http://orcid.org/0000-0002-1263-6300 1 http://mml.spbstu.ru/seqopt/ 1 http://dx.doi.org/10.7717/ 1 http://doi.org/10 1 http://creat 1 http://clinicaltrials.gov 1 http://AdZ.cf.ac.uk Top 50 email addresses; "Who are you gonna call?" ------------------------------------------------- 33 tgartner@vub.ac.be 33 stasa@hol.gr 33 rnsr@studmed.au.dk 33 michael.siassi@rzmail.uni-erlangen.de 33 judit.wefer@cmm.ki.se 1 smdmacedo@yahoo.com.br 1 pdumbauld@live.com 1 mone@usp.br 1 maarbos@ir.vhebron.net 1 hzwickey@nunm.edu 1 hiwasaka@med.oita-u.ac.jp 1 h.schellekens@gdl.uu.nl 1 drwpruzanski@bellnet.ca 1 bdangerfield@nunm.edu 1 ann.pettersson@hik.se Top 50 positive assertions; "What sentences are in the shape of noun-verb-noun?" ------------------------------------------------------------------------------- 70 levels were significantly 66 levels were higher 46 treatment did not 45 genes were significantly 41 cells was significantly 40 activity was not 40 expression did not 36 response was not 35 cells have not 35 groups was comparable 34 cell mediated disease 34 cells are cells 34 cells have long 34 cells was severely 34 disease had significantly 34 infection are surprisingly 34 levels were predictive 34 proteins using mutagenesis 34 responses following acute 34 studies involving skin 33 activation have so 33 cells express icosl 33 cells showed only 33 expression is similar 33 levels are predictive 33 levels were subsequently 33 macrophages are capable 33 macrophages induce tumour 33 macrophages was closely 33 patients expressed significantly 33 patients had significant 33 response was further 33 responses were about 33 study involved longitudinal 30 cells were then 26 group were significantly 22 levels were not 16 expression was significantly 16 levels did not 15 effect was not 15 levels were also 14 cells are not 14 cells did not 14 group was significantly 13 cells are also 13 cells is not 12 cells were also 12 expression was not 11 cells are able 11 cells do not Top 50 negative assertions; "What sentences are in the shape of noun-verb-no|not-noun?" --------------------------------------------------------------------------------------- 34 proteins showed no difference 33 activity was not predictive 33 response was not compromised 4 levels were not significantly 3 cells is not only 3 expression was not significantly 3 treatment had no effect 2 activation results not only 2 cells are not only 2 cells were not able 2 controls were not different 2 effect is not direct 2 effects were not due 2 levels were not different 2 levels were not statistically 2 results showed no difference 2 tnf had no effect 2 tnf has no direct 1 % had no detectable 1 activation are not well 1 activation is not dependent 1 activation was not biphasic 1 activities are not well 1 activity is not clearly 1 activity is not co 1 activity is not essential 1 activity is not obligatory 1 activity was not different 1 activity was not necessary 1 blood is not reflective 1 cells are not critical 1 cells are not fully 1 cells are not necessary 1 cells are not preponderant 1 cells are not primary 1 cells are not usually 1 cells are not yet 1 cells did not significantly 1 cells do no longer 1 cells do not phagocytose 1 cells do not usually 1 cells is not available 1 cells is not comprehensively 1 cells is not dependent 1 cells is not due 1 cells is not necessary 1 cells is not well 1 cells is not yet 1 cells produced no tnf 1 cells showed no immuno A rudimentary bibliography -------------------------- id = cord-013803-d1sbfibq author = Abu El-Asrar, Ahmed M. title = Soluble cytokine receptor levels in aqueous humour of patients with specific autoimmune uveitic entities: sCD30 is a biomarker of granulomatous uveitis date = 2019-12-05 keywords = CD30; TNF; VKH summary = title: Soluble cytokine receptor levels in aqueous humour of patients with specific autoimmune uveitic entities: sCD30 is a biomarker of granulomatous uveitis Previous studies demonstrated upregulation of proinflammatory cytokines, such as tumour necrosis factor-α (TNF-α), interferon-γ (IFN-γ), interleukin (IL)-6, IL-15 and IL-17 in the aqueous humour (AH) samples from autoimmune uveitis patients [1] [2] [3] [4] [5] . For these reasons, we analyzed the AH from patients with active uveitis associated with four systemic inflammatory diseases (sarcoidosis, VKH disease, BD and HLA-B27-related inflammation) for the presence of sCD30, sCD163, sgp130, sIL-6R, sTNFRI and sTNFRII. Compared with controls, TNF-α, sCD163, sgp130, sIL-6R, sTNFRI and sTNFRII levels were significantly higher in BD and HLA-B-27-associated uveitis. Among the cytokine and soluble cytokine receptors analyzed, TNF-α and sCD30 differed significantly between patients with BD, sarcoidosis, HLA-B27-associated uveitis and VKH disease (p = 0.029; p = 0.001, respectively) (Fig. 1a) . doi = 10.1038/s41433-019-0693-7 id = cord-023403-jzdrvfvr author = Ahlfors, E. title = Proliferation of Cells in the Oral Mucosa, the Ear Skin and the Regional Lymph Nodes in Mice Sensitized and Elicited with a Hapten date = 2008-06-28 keywords = CD8; IFN; IL-12; MBL; TNF; cell summary = doi = 10.1111/j.0300-9475.2004.01423ac.x id = cord-272695-wmzq4lkh author = Ahmed, Ahmed A. title = TNF-α − 308 G/A and IFN-γ + 874 A/T gene polymorphisms in Saudi patients with cutaneous leishmaniasis date = 2020-05-13 keywords = IFN; TNF summary = This study was undertaken to test the association of TNF-α − 308 and IFN-γ + 874 gene polymorphisms with the susceptibility of Leishmania (L) species among CL patients in central region of Saudi Arabia. The amplified PCR product for TNF-α-308 was detected at 184 base pair as shown in Fig. 1 , based on these results, different species of CL, the genotypes and the alleles of the host genes polymorphism were determined and evaluated in comparison with their respective healthy controls (supplementary file (Table 3 ). The amplified PCR product for IFN-γ + 874 were detected at 263 base pair as shown in Fig. 2 , based on these results, different species of CL, the genotypes and the alleles of the host genes polymorphism were determined and evaluated in comparison with their respective healthy controls. doi = 10.1186/s12881-020-01043-9 id = cord-023375-x4p187u7 author = Alitalo, A. title = Lysine‐Dependent Binding of OspE to the C‐terminus of Factor H Mediates Complement Resistance in Borrelia burgdorferi date = 2008-06-28 keywords = CD8; IFN; IL-12; MBL; TNF; cell summary = We demonstrate that Cw6 þ psoriasis patients had significant CD8 þ T-cell IFN-g responses to peptides from K17 and M6 protein selected on the basis of sequence homology and predicted HLA-Cw*0602 binding. The uptake of MBP by B cells and the presentation of MBP-derive peptides to T helper (Th) cells by B cells may be promoted by the formation of complement (C) activating immune complexes (ICs) between MBP and natural autoantibodies in healthy individuals and disease-associated anti-MBP antibodies in MS patients, respectively. While MBP did not induce measurable proliferation of B cells nor CD4 þ T cells, we observed the production of TNF-a, IFN-g and IL-10 by PBMC in response to incubation with MBP in the presence of sera from healthy controls as well as sera from MS patients. In conclusion, the results of this study suggest an involvement of the ASMase in the activation, expansion or maturation of virus-specific CD8 þ T cells during the acute infection of mice with the LCM virus. doi = 10.1111/j.0300-9475.2004.01423aj.x id = cord-271114-hv3gwvdi author = Allam, Gamal title = Neonatal infections in Saudi Arabia: Association with cytokine gene polymorphisms date = 2015-04-22 keywords = EOS; IFN; IL-6; TNF summary = The objective of this study was to investigate single nucleotide polymorphism (SNP) in the interleukin (IL)-1β –31 T/C, IL-6 –174 G/C, tumor necrosis factor α (TNF-α) –308 G/A, and interferon γ (IFN-γ) +874 A/T genes for their possible association with susceptibility to early onset sepsis (EOS) in Saudi newborn infants. Our results show that the circulating IL-1β, IL-6, TNF-α, and IFN-γ were significantly (p < 0.001) elevated in EOS patients compared to suspected and sepsis-free control groups; and IL-1β –31C, IL-6 –174G, TNF-α –308G, and IFN-γ +874A alleles were associated with EOS in Saudi infants. Therefore, the primary aim of the current study was to investigate SNPs in the IL-1β -31 T/C (rs1143643), IL-6 -174 G/C (rs1800795), TNF-α -308 G/A (rs1800629), and IFN-γ +874 A/T (rs2430561) genes for their possible association with susceptibility to EOS in Saudi newborn infants. Newborns with sepsis had significantly higher serum levels of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α, and IFN-γ) compared to both suspected and sepsis-free control groups (overall p value < 0.001, Table 1 ). doi = 10.5114/ceji.2015.50836 id = cord-017470-sjk7a34u author = Arlati, Sergio title = Pathophysiology of Acute Illness and Injury date = 2018-06-14 keywords = SIRS; TNF; car; cell; cytokine; increase; inflammatory; sepsis; tissue summary = doi = 10.1007/978-3-319-95114-0_2 id = cord-023411-iszb5qlk author = Astrinidou‐Vakaloudi, A. title = Presence of Helicobacter pylori Antibodies in Haemodialysis Patients date = 2008-06-28 keywords = CD8; IFN; IL-12; MBL; TNF; cell summary = doi = 10.1111/j.0300-9475.2004.01423p.x id = cord-004919-d7tilk8v author = Baker, Rahaf title = Macrophage activation syndrome in a patient with axial spondyloarthritis on adalimumab date = 2018-12-07 keywords = MAS; TNF summary = MAS is a potentially fatal syndrome that can present in patients with inflammatory conditions and is considered to be similar to hemophagocytic lymphohistiocytosis (HLH) [1, 2] . The most consistent diagnosis for our patient was MAS, as he had high persistent fevers without an infectious cause, lymphopenia and anemia, marked hyperferritinemia, hypertriglyceridemia, splenomegaly, and the presence of hemophagocytes on bone marrow biopsy. It is plausible that adalimumab triggered MAS in our patient as he presented at 2.5 months after initiation of adalimumab, which is consistent with the timeline from other case reports, and he had no obvious infection. Macrophage activation syndrome associated with etanercept in a child with systemic onset juvenile idiopathic arthritis Macrophage activation syndrome following initiation of etanercept in a child with systemic onset juvenile rheumatoid arthritis Visceral leishmaniasis and macrophagic activation syndrome in a patient with rheumatoid arthritis under treatment with adalimumab Possible macrophage activation syndrome following initiation of adalimumab in a patient with adult-onset still''s disease doi = 10.1007/s10067-018-4387-5 id = cord-013183-t25gecuw author = Beloumi, Dhekra title = Inflammatory Correlated Response in Two Lines of Rabbit Selected Divergently for Litter Size Environmental Variability date = 2020-09-01 keywords = TNF; high; line summary = The aim of this study was to evaluate the inflammatory response in the two lines of the experiment, in order to analyse the effect of selection on susceptibility to diseases after challenging to stressful situations, such as 24 h after the first delivery. The line selected for litter size heterogeneity (the high line) showed lower white blood leukocyte count (WBC; −0.87 × 10(3)/µL), lower percentage of basophils (−0.11%), higher concentration of TNF-α (+13.8 pg/mL), and greater concentration of CRP (+38.1 µg/mL) than the line selected for litter size homogeneity (the low line). The objective of this study was to evaluate the inflammatory response in the two lines of the divergent selection experiment for litter size environmental variance, in order to analyse the effect of selection on susceptibility to diseases after stressful situations, such as 24 h after the first delivery. doi = 10.3390/ani10091540 id = cord-016960-xhzvp35g author = Berencsi, György title = Fetal and Neonatal Illnesses Caused or Influenced by Maternal Transplacental IgG and/or Therapeutic Antibodies Applied During Pregnancy date = 2012-03-08 keywords = CTLA-4; Nieri; SLE; TNF; antibody; cell; disease; neonatal; patient; pregnancy; treatment summary = The importance of maternal anti-idiotypic antibodies are believed to prime the fetal immune system with epitopes of etiologic agents infected the mother during her whole life before pregnancy and delivery. Neonatal lupus is a model of passively acquired autoimmunity in which a mother-, who may have systemic lupus erythematosus (SLE) or Sj€ ogren''s syndrome (SS) or may be entirely asymptomatic-synthesizes antibodies to SSA/Ro and/or SSB/ La ribonucleoproteins that enter the fetal circulation via trophoblast FcRn receptors and presumably cause tissue injury (Lee 1990 ) as mentioned above. Teplizumab (CD3-specific, hOKT3g1-Ala-Ala), a humanized Fc mutated anti-CD3 monoclonal antibody induced tolerance, on the progression of type 1 diabetes in patients with recent-onset disease even 2 years after the first diagnosis (Herold et al. Clinical and immune responses in resected colon cancer patients treated with anti-idiotype monoclonal antibody vaccine that mimics the carcinoembryonic antigen Clinical use of anti-CD25 antibody daclizumab to enhance immune responses to tumor antigen vaccination by targeting regulatory T cells doi = 10.1007/978-94-007-4216-1_9 id = cord-023390-5hcgdlmt author = Bhuvanath, S. title = Inflammatory Cytokine Modulation of Cancer Cell Proliferation date = 2008-06-28 keywords = CD8; IFN; IL-12; MBL; TNF; cell summary = doi = 10.1111/j.0300-9475.2004.01423bi.x id = cord-310942-191m0e65 author = Boga, Jose Antonio title = Beneficial actions of melatonin in the management of viral infections: a new use for this “molecular handyman”? date = 2012-04-18 keywords = IFN; TNF; cell; infection; melatonin; virus summary = The potential protective mechanisms include melatonin acting as a free radical scavenger, an antioxidant enzyme inducer, a positive regulator of immune functions and an inhibitor of inflammation, as well as a regulator of programmed cell death (PCD) [ Table 2 ]. Melatonin treatment also caused a rise in protein expression of the nuclear factor erythroid 2 (Nrf2), a transcription factor that plays a critical role by binding to the antioxidant response element in the promoter region of a number of genes encoding for antioxidant and detoxifying enzymes in several types of cells and tissues [109] . Respiratory syncytial virus infection of human respiratory epithelial cells enhances inducible nitric oxide synthase gene expression Melatonin decreases nitric oxide production and lipid peroxidation and increases interleukin-1 beta in the brain of mice infected by the Venezuelan equine encephalomyelitis virus doi = 10.1002/rmv.1714 id = cord-351310-6p42b144 author = Bohr, Adam title = Treatment of acute lung inflammation by pulmonary delivery of anti-TNF-α siRNA with PAMAM dendrimers in a murine model date = 2020-08-13 keywords = LPS; PAMAM; TNF summary = In this study, commercially available generation 3 poly(amidoamine) (PAMAM) dendrimer was investigated for pulmonary delivery of siRNA directed against tumor necrosis factor (TNF) α for the treatment of acute lung inflammation. Delivery efficiency was assessed in vitro in the RAW264.7 macrophage cell line activated with lipopolysaccharide (LPS), and efficacy was evaluated in vivo in a murine model of LPS-induced lung inflammation upon pre-treatment with TNF-α siRNA. Also in vivo, the PAMAM dendriplexes induced efficacious TNF-α siRNA inhibition, as compared to non-complexed siRNA, upon pulmonary administration to mice with LPS-induced lung inflammation. In this study, we investigated generation 3 PAMAM dendrimers as transfection agents for pulmonary delivery of siRNA targeting TNF-α and examined their efficacy and safety in a murine acute lung inflammation model. Generation 3 PAMAM dendrimers were selected because they display very good efficiency for dendriplex formation They were prepared at different dendrimer-siRNA ratios and were characterized in vitro and in vivo concerning complexation, cellular uptake, cytotoxicity, in vitro transfection efficiency and in vivo therapeutic efficacy at the RNA and protein levels, respectively. doi = 10.1016/j.ejpb.2020.08.009 id = cord-337414-8ndkjs1i author = Burgmaier, Gruscha title = Association of Increased Bcl‐2 Expression with Rescue from Tumor Necrosis Factor‐α‐Induced Cell Death in the Oligodendrocyte Cell Line OLN‐93 date = 2008-07-29 keywords = Bcl-2; OLN; TNF-; cell summary = doi = 10.1046/j.1471-4159.2000.0752270.x id = cord-006518-al94gxjw author = Calder, Philip C. title = n−3 Fatty acids, inflammation, and immunity— Relevance to postsurgical and critically III patients date = 2004 keywords = TNF; acid; effect; fatty; fish; oil; patient summary = More recent studies showed that EPA did not induce TNF-α, IL-1β, or IL-1α (68) or IL-6 (69) in osteoblasts, and even countered the upregulating effect of arachidonic acid (68) ; that EPA and DHA could totally abolish cytokine-induced up-regulation of TNF-α, IL-1α, and IL-1β in cultured bovine chondrocytes and in human osteoarthritic cartilage explants (93, 94) ; and that EPA or fish oil inhibited endotoxin-induced TNF-α production by monocytes (111) (112) (113) (114) . Animal feeding studies with fish oil support the observations made in cell culture with respect to the effects of long-chain n-3 FA on NFκB activation and inflammatory cytokine production. Several studies in humans involving supplementation of the diet with fish oil have demonstrated decreased production of TNF-α, IL-1β, and IL-6 by endotoxin-stimulated monocytes or mononuclear cells (a mixture of lymphocytes and monocytes) (80) (81) (82) 119) . doi = 10.1007/s11745-004-1342-z id = cord-001293-dfaxj3bv author = Cavaillon, Jean-Marc title = Is boosting the immune system in sepsis appropriate? date = 2014-03-24 keywords = TNF; patient; sepsis summary = In response to the failure of therapies aiming to target either the up-stream microbial activators or the effector molecules of the inflammatory cascade, a new concept has emerged of boosting the immune system to counter immunosuppression that develops in patients who survive the initial, hyperinflammatory period of sepsis [1] . One can conjecture that systemic treatment with IL-7 may act in undesired places, as illustrated by the following: IL-7 worsens graft-versus-host-induced tissue inflammation [81] ; favors inflammation in colitis [82] , contributes to arthritis severity [83] ; upregulates chemokines, IFNγ, macrophage recruitment, and lung inflammation [84] ; and, finally, increases production of inflammatory cytokines by monocytes and T cells [85] . Not only are PD-1-deficient mice markedly protected from the lethality of sepsis, accompanied by a decreased bacterial burden and suppressed inflammatory cytokine response [98] , but also blockade of PD-1 or PD-L1 improves survival in a murine model of sepsis, reverses immune dysfunction, inhibits lymphocyte apoptosis, and attenuates organ dysfunction [99] [100] [101] . doi = 10.1186/cc13787 id = cord-316904-g7dli0a8 author = Chang, Hernan R. title = Role of cytokines in AIDS wasting date = 1998-12-31 keywords = AIDS; HIV; IL-1; IL-6; TNF summary = Indeed, although wasting is not universally observed in AIDS patients, the wasting syndrome in a human immunodeficiency virus (HIV)-seropositive individual is generally utilized to establish the diagnosis of AIDS 1 and is defined by a decrease in body mass greater than 10% in the absence of concomitant opportunistic infections, malignancies, and other identifiable causes of weight loss. 33 It is against this background presentation of the interacting factors contributing to malnutrition and functional impairment in HIVinfected patients-namely anorexia, malabsorption, hypermetabolism, lethargy, and impaired fat and protein metabolism-that the role of cytokines in the AIDS wasting syndrome is discussed in the following sections. In addition to their pleiotropic actions on many body systems, they could potentially contribute to the wasting and cachexia of AIDS by their ability to induce anorexia, alter energy expenditure, increase muscle proteolysis and net protein breakdown, and initiate various abnormalities of lipid metabolism. doi = 10.1016/s0899-9007(98)00108-7 id = cord-339272-trd6rkxw author = Chen, Na title = Prime-O-glucosylcimifugin attenuates lipopolysaccharide-induced acute lung injury in mice date = 2013-04-24 keywords = LPS; Prime; TNF summary = The purpose of this study was to evaluate the effect of prime-O-glucosylcimifugin on acute lung injury (ALI) induced by lipopolysaccharide in mice. LPS-induced ALI is considered a neutrophil-dependent ALI that contributes to local recruitment and activation of neutrophils [8] ; the release of pro-inflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6; and the formation of reactive oxygen and nitrogen species [9] [10] [11] . Therefore, with a mouse model of acute lung inflammation, the present study was undertaken to examine the effect of Prime-O-glucosylcimifugin on acute lung injury induced by intranasal instillation of LPS in BALB/c mice and investigate its possible mechanisms. Acute lung injury is characterized by systemic airway inflammatory response including cytokines (e.g., TNF-α, IL-6, IL-8), chemokines, pro-inflammatory mediators and a variety of cells, which regulate the migration and pulmonary infiltration of neutrophils into the interstitial tissue [34] . doi = 10.1016/j.intimp.2013.04.014 id = cord-023414-xxw5kptr author = Chistensen, H. R. title = Characterization of a Large Panel of Lactic Acid Bacteria Derived from the Human Gut for their Capacity to Polarize Dendritic Cell date = 2008-06-28 keywords = CD8; IFN; MBL; TNF; cell; lactobacillus summary = We demonstrate that Cw6 þ psoriasis patients had significant CD8 þ T-cell IFN-g responses to peptides from K17 and M6 protein selected on the basis of sequence homology and predicted HLA-Cw*0602 binding. The uptake of MBP by B cells and the presentation of MBP-derive peptides to T helper (Th) cells by B cells may be promoted by the formation of complement (C) activating immune complexes (ICs) between MBP and natural autoantibodies in healthy individuals and disease-associated anti-MBP antibodies in MS patients, respectively. While MBP did not induce measurable proliferation of B cells nor CD4 þ T cells, we observed the production of TNF-a, IFN-g and IL-10 by PBMC in response to incubation with MBP in the presence of sera from healthy controls as well as sera from MS patients. In conclusion, the results of this study suggest an involvement of the ASMase in the activation, expansion or maturation of virus-specific CD8 þ T cells during the acute infection of mice with the LCM virus. doi = 10.1111/j.0300-9475.2004.01423ap.x id = cord-330549-ppuqvafd author = Christophi, George P. title = Macrophages of multiple sclerosis patients display deficient SHP-1 expression and enhanced inflammatory phenotype date = 2009-04-27 keywords = SHP-1; TNF; macrophage; stat1 summary = Supporting a direct role of SHP-1 deficiency in altered macrophage function, experimental depletion of SHP-1 in normal subject macrophages resulted in an increased STAT/NF-κB activation and increased inflammatory gene expression to levels seen in macrophages of MS patients. Supporting a direct role of SHP-1 deficiency in altered macrophage function, experimental depletion of SHP-1 in macrophages of normal human subjects using siRNA resulted in an increased activation of the above transcription factors and increased inflammatory gene expression to levels seen in macrophages of MS patients. In order to determine whether increased activation of STAT6, STAT1, and NF-κB in macrophages of MS patients relative to normal subjects corresponded to heightened expression of STAT6-, STAT1-, and NF-κB responsive genes, the mRNA levels of several genes were quantified following 18-hour treatment with several cytokines (Figure 6 ). doi = 10.1038/labinvest.2009.32 id = cord-018764-02l423mk author = Clark, Ian A. title = The molecular basis of paediatric malarial disease date = 2007 keywords = Plasmodium; TNF; african; falciparum; malaria; severe summary = The influence of inflammatory cytokines on cellular function offers a molecular framework to explain the multiple clinical syndromes that are observed during acute malarial illness, and provides a fresh avenue of investigation for adjunct therapies to ameliorate the malarial disease process. The presence of hyperlactataemia, hypoglycaemia, and metabolic acidosis, all three consistent with a patient being forced to rely on anaerobic glycolysis for energy production, have provided a consensus that hypoxia is central to disease pathogenesis in falciparum malaria. Another inflammatory cytokine, macrophage inhibitory factor (MIF) that is increased in malaria, and induced by TNF, has been shown to cause dyserythropoiesis in in vitro studies on bone marrow cells [95, 96] . Although the sepsis world now discusses several origins for the lactate increase, including inflammation-induced mitochondrial dysfunction [97] , in falciparum malaria it is still generally attributed to a reduced oxygen supply, mostly through microvascular occlusion by sequestered parasitised erythrocytes [121] . doi = 10.1007/978-3-7643-8099-1_9 id = cord-355847-1ru15s5a author = Convertino, Irma title = Exploring pharmacological approaches for managing cytokine storm associated with pneumonia and acute respiratory distress syndrome in COVID-19 patients date = 2020-06-11 keywords = ARDS; COVID-19; TNF summary = Several drugs, endowed with modulating activity on cytokine pathways, including anti-IL-6, anti-TNF, and Janus kinase (JAK) inhibitors, currently approved for the treatment of immune-mediated inflammatory diseases, have been suggested or could be yet taken into account for experimental use in COVID-19 patients with ARDS and/or pneumonia ( Fig. 1 ). In addition, a multicenter open-label randomized clinical trial is studying the benefit risk profile of siltuximab, as a single therapeutic option or in combination with anakinra, at a single dose of 11 mg/kg, in comparison with tocilizumab or anakinra, alone or in combination, in ARDS patients with COVID-19 [20] . Based on the results expected with tocilizumab and siltuximab, other anti-IL-6 drugs, currently approved for rheumatoid arthritis, namely sarilumab and sirukumab, could be studied in ARDS and pneumonia patients with COVID-19. Anti-JAK drugs (such as ruxolitinib, tofacitinib, baricitinib, oclacitinib, fedratinib, upadacitinib, and peficitinib) [39] should be considered also among the options for clinical investigations in COVID-19-related ARDS and pneumonia patients. doi = 10.1186/s13054-020-03020-3 id = cord-317628-1inxq7t5 author = Cuccarese, Michael F. title = Functional immune mapping with deep-learning enabled phenomics applied to immunomodulatory and COVID-19 drug discovery date = 2020-08-14 keywords = COVID-19; Fig; SARS; TGF; TNF; Thermo; cell; compound summary = We deploy the platform to develop phenotypic models of active SARS-CoV-2 infection and of COVID-19-associated cytokine storm, surfacing compounds with demonstrated clinical benefit and identifying several new candidates for drug repurposing. We used these capabilities to rapidly develop high-throughput-ready disease models for both SARS-CoV-2 viral infection and the resulting cytokine storm, and immediately launched large-scale drug screens that recapitulated known effective and ineffective therapies and, more importantly, identified several new potential treatments for both SARS-CoV-2 infection and COVID-19-associated cytokine storm. To define the model, we evaluated the effect of SARS-CoV-2 infection in multiple cell types, of which three resulted in robust phenoprints as compared to either mock infected or inactivated virus control populations: Calu3 (a lung adenocarcinoma line), Vero (an immortalized interferondeficient African green monkey kidney line 55 ), and primary Human Renal Cortical Epithelium (HRCE) (Fig. 5C, Fig. S6D ). doi = 10.1101/2020.08.02.233064 id = cord-309171-kgc7lgjp author = Dolinger, Michael T. title = Pediatric Crohn''s Disease and Multisystem Inflammatory Syndrome in Children (MIS-C) and COVID-19 Treated with Infliximab date = 2020-05-21 keywords = TNF; covid-19 summary = We describe a case of severe COVID-19 infection in a recently diagnosed pediatric Crohn''s disease patient successfully treated with Tumor Necrosis Factor-alpha (TNF-α) blockade. Cytokine profile revealed rising levels of interleukin (IL)-6, IL-8, and TNF-α, higher than those described in either inflammatory bowel disease (IBD) or severe COVID-19 alone. The patient was treated with infliximab for TNF-α blockade to address both moderately to severely active Crohn''s disease and multisystem inflammatory syndrome in children (MIS-C) temporally related to COVID-19. 2 We describe a pediatric patient recently diagnosed with Crohn''s disease who developed severe COVID-19 infection successfully treated with infliximab. This is the first reported case of a patient with recently diagnosed Crohn''s disease with suspected MIS-C temporally related to COVID-19 treated with infliximab to co-manage both entities. doi = 10.1097/mpg.0000000000002809 id = cord-309619-glb2y82u author = Domingo, Pere title = The four horsemen of a viral Apocalypse: The pathogenesis of SARS-CoV-2 infection (COVID-19) date = 2020-07-29 keywords = ACE2; Ang; COVID-19; IFN; SARS; TNF summary = Severe acute respiratory syndrome (SARS)-coronavirus (CoV)-2 lights the wick by infecting alveolar epithelial cells (AECs) and downregulating the angiotensin converting enzyme-2 (ACE2)/angiotensin (Ang-1–7)/Mas1R axis. SARS-CoV induces the signal transducer and activator of transcription 1 TACE TNF-a converting enzyme TBK1 TANK-binding kinase 1 TLR toll-like receptor TMPRSS2 type II transmembrane serine protease TNF-a tumor necrosis alpha TRAF3 TNF receptor-associated factor 3 XCR1 XCL1 (Chemokine [C motif] ligand 1) and XCL3 (Chemokine [C motif] ligand 3) receptor production of double-membrane vesicles that lack PRRs and can then replicate in these vesicles [18] . COVID-19 patients have high serum levels of inflammatory cytokines, including interleukin (IL)-2, IL-7, IL-10, granulocyte-colony stimulating factor (G-CSF), interferon gamma-induced protein (IP)-10, monocyte chemoattractant protein (MCP)-1, macrophage SARS-CoV-2 infects primarily type II pneumocytes through binding to the ACE2 receptor. ACE2 = Angiotensin-converting enzyme 2; SARS-CoV-2 = Severe acute respiratory syndrome coronavirus 2; Ang II = Angiotensin II; ROS = Reactive oxygen species; AT1R = Angiotensin 1 receptor; ADAM17 = A disintegrin and metalloproteinase domain 17; TNF-a = Tumor necrosis factor alpha; TMPRSS2 = transmembrane protease serine 2. doi = 10.1016/j.ebiom.2020.102887 id = cord-023441-q83y12sk author = Draborg, H. title = Recominant Expression and Immunological Characterization of House Dust Mite Allergen Der P 1 date = 2008-06-28 keywords = CD8; IFN; IL-12; MBL; TNF; cell summary = We demonstrate that Cw6 þ psoriasis patients had significant CD8 þ T-cell IFN-g responses to peptides from K17 and M6 protein selected on the basis of sequence homology and predicted HLA-Cw*0602 binding. The uptake of MBP by B cells and the presentation of MBP-derive peptides to T helper (Th) cells by B cells may be promoted by the formation of complement (C) activating immune complexes (ICs) between MBP and natural autoantibodies in healthy individuals and disease-associated anti-MBP antibodies in MS patients, respectively. While MBP did not induce measurable proliferation of B cells nor CD4 þ T cells, we observed the production of TNF-a, IFN-g and IL-10 by PBMC in response to incubation with MBP in the presence of sera from healthy controls as well as sera from MS patients. In conclusion, the results of this study suggest an involvement of the ASMase in the activation, expansion or maturation of virus-specific CD8 þ T cells during the acute infection of mice with the LCM virus. doi = 10.1111/j.0300-9475.2004.01423ag.x id = cord-005983-2ascbu62 author = Eigler, A. title = Suppression der Synthese des Tumornekrosefaktors date = 2001 keywords = Hemmung; Synthese; TNF; der; die summary = Klinische Studien aus den vergangenen 5 Jahren belegen die zentrale Rolle des Tumornekrosefaktors (TNF) im pathophysiologischen Geschehen der rheumatoiden Arthritis und des Morbus Crohn.Die vorliegende Arbeit gibt einen Überblick über die Regulation der Synthese und die vielfältigen Wirkungen dieses Zytokins.So wurden erhöhte TNF-Konzentrationen bei verschiedenen infektiösen und entzündlichen Erkrankungen sowie in Verbindung mit speziellen Therapien nachgewiesen.Darauf aufbauend werden experimentelle therapeutische Strategien zur Hemmung der TNF-Bildung dargestellt. In den folgenden Abschnitten wird näher auf Strategien zur Hemmung der TNF-Synthese eingegangen, die im Tierexperiment oder schon beim Menschen in klinischen Studien untersucht worden sind. Die entzündungshemmende Wirkung von cAMP-erhöhenden Substanzen wird jedoch nicht nur über eine Hemmung der TNF-Synthese vermittelt. Weiterhin konnte durch die Therapie mit Rolipram die Suppression der TNF-Synthese und ein Überlebensvorteil in einem Rattenmodell des ARDS gezeigt werden [40] . The specific type IV phosphodiesterase inhibitor rolipram suppresses tumor necrosis factor-α production by human mononuclear cells doi = 10.1007/s001080050721 id = cord-021266-afs9eb40 author = El Gendy, Fady M. title = The role of Tumor necrosis factor alpha −308 G>A promoter polymorphism in pediatric community acquired pneumonia date = 2020-02-10 keywords = TNF; cap summary = Our objective was to evaluate the association of TNF-α gene −308 G>A polymorphism with susceptibility to, and severity of, community-acquired pneumonia (CAP). We found no significant association of alleles or genotypes with any indicators of CAP severity, including clinical severity scores, but we were not able to assess the influence of TNF-α polymorphism on mortality since none of our patients died. Consistent with our findings, genotyping of 77 children with respiratory syncytial virus infection revealed no association of TNF-α −308 G>A polymorphism with any of the clinical outcomes, including severity scores of lower respiratory illness, oxygen saturation, lengths of oxygen supplementation, intensive care unit (ICU) and hospital stays, and the presence or absence of pneumonia and otitis media [25] . However, another study of 277 Chinese adult patients with severe pneumonia-induced sepsis found that TNF-α "A" allele increased the risk of septic shock (OR = 4.28). doi = 10.1186/s43054-020-0019-1 id = cord-017639-wtc8bml5 author = El-Radhi, A. Sahib title = Pathogenesis of Fever date = 2019-01-02 keywords = IL-1; TNF; fever summary = The induction of fever results in inhibition of bacterial growth, increased bactericidal effects of neutrophils, production of acute-phase protein synthesis and other physiological changes such as anorexia and somnolence. • Cytokines are proteins produced throughout the body, mainly by activated macrophages, monocytes and T cells to regulate the immune responses within the body, control inflammatory and haematopoietic processes and may induce fever. Pro-inflammatory cytokines (e.g. IL-1, IL-6, TNF-α, INF-γ, granulocytes-macrophages colony stimulating factor, GM-CSF) are responsible for initiating an effective defence against exogenous organisms (e.g. activating neutrophils). • Exogenous pyrogens initiate fever by inducing host cells (primarily macrophages) to produce and release endogenous pyrogens such as interleukin-1, which has multiple biological functions essential for the immune response. • Exogenous pyrogens initiate fever by inducing host cells (primarily macrophages) to produce and release endogenous pyrogens such as interleukin-1, which has multiple biological functions essential for the immune response. doi = 10.1007/978-3-319-92336-9_3 id = cord-336510-qzm9wgde author = Ellermann-Eriksen, Svend title = Macrophages and cytokines in the early defence against herpes simplex virus date = 2005-08-03 keywords = HSV; IFN; IL-12; IL-4; TNF; cell; infection; virus summary = In a first wave of responses, cytokines, primarily type I interferons (IFN) and tumour necrosis factor are produced and exert a direct antiviral effect and activate the macrophages themselves. Generally the type I IFNs exhibit a huge range of biological effects, such as antiviral and antiproliferative effects, stimulation of immune cells such as T cells, natural killer (NK) cells, monocytes, macrophages, and dendritic cells, increased expression of MHC-I, activation of pro-apoptotic genes and inhibition of anti-apoptotic mechanisms, modulation of cellular differentiation, and inhibition of angiogenesis [171] . Effect of IL-4 and IL-13 on IFN-gamma-induced production of nitric oxide in mouse macrophages infected with herpes simplex virus type 2 Herpes Simplex virus type 1-induced interferon production and activation of natural killer cells in mice NF-kappaB activation is responsible for the synergistic effect of herpes simplex virus type 2 infection on interferon-gamma-induced nitric oxide production in macrophages doi = 10.1186/1743-422x-2-59 id = cord-256838-8rzibpbl author = Eng, Yi Shin title = Unraveling the Molecular Mechanism of Traditional Chinese Medicine: Formulas Against Acute Airway Viral Infections as Examples date = 2019-09-27 keywords = GGT; IFN; MXGST; TCM; TNF; Tang; effect summary = There are still issues regarding the conflicting pharmacologic effects, pharmacokinetics, drug interactions, adverse and clinical effects of herbal medicine and TCM. Several factors may affect the molecular mechanisms and subsequent clinical effects of TCM formulas, including individual gene-based response, composition and amount of active molecules in TCM formulas, complex interactions, and appropriateness of use of TCM formulas. From the viewpoint of pathophysiology, TCM formulas used to manage airway viral infections need to have antiviral activity against such viruses listed above, and/or to induce antiviral cytokines, and/or anti-inflammatory effect, and/or to relieve symptoms commonly presented in airway infections ( Figure 1 ). To simplify the molecular mechanisms and to correlate the pharmacologic activities with their clinical effects, five formulas of A-physicians will be used as examples against airway infections: Several health benefits of herbal medicine and TCM are claimed; for example, herbs and TCM formulas, including those discussed above, are believed to have anti-oxidative activities helpful against several diseases. doi = 10.3390/molecules24193505 id = cord-270414-gh9agf4x author = Fischer, Y. title = Randomized, Placebo Controlled Study of the Effect of Propentofylline on Survival Time and Quality of Life of Cats with Feline Infectious Peritonitis date = 2011-10-12 keywords = FIP; PPF; PTX; TNF summary = title: Randomized, Placebo Controlled Study of the Effect of Propentofylline on Survival Time and Quality of Life of Cats with Feline Infectious Peritonitis Several case reports can be found in the online Veterinary Information Network (http://www.VIN.com) that describe a positive effect of the methylxanthine derivative pentoxifylline (PTX) (Trental a ) on the survival time in cats with FIP. ALT alanine aminotransferase AP alkaline phosphatase CI confidence interval FCoV feline coronavirus FeLV feline leukemia virus FIP feline infectious peritonitis FIPV feline infectious peritonitis virus FIV feline immundeficiency virus IFAT immunofluorescent antibody technique PPF propentofylline PTX pentoxifylline RBC red blood cells SPSS statistical package for the social sciences TNF-a tumor necrosis factor-alpha TP total protein WBC white blood cells which cause endothelial cell damage. The aim of this study was to evaluate the efficacy of PPF on the survival time and quality of life in cats with a confirmed diagnosis of FIP in a placebocontrolled double-blind trial. doi = 10.1111/j.1939-1676.2011.00806.x id = cord-016523-pznw2ciu author = Fouqué, Amélie title = The CD95/CD95L Signaling Pathway: A Role in Carcinogenesis date = 2014-08-29 keywords = CD95; FADD; Fas; TNF; cell; signal summary = During interactions with respective ligands, members of the death receptor superfamily recruit adaptor proteins such as Fas-associating protein with a death domain (FADD) [ 7 , 8 ] or tumor necrosis factor (TNF) receptor 1-associated death domain protein (TRADD) [ 9 ] , resulting in the aggregation and activation of the initiator caspase-8 and caspase-10 to form the death-inducing signaling complex (DISC) [ 10 ] . These type I transmembrane proteins share common features, such as extracellular amino-terminal cysteine-rich domains (CRDs) [ 19 , 20 ] , which contribute to ligand specifi city [ 21 ] , and preassociation of the receptor at the plasma membrane [ 22 -24 ] and a conserved 80 amino acid sequence located in their cytoplasmic tail called death domain (DD), which is necessary for DISC formation and initiation of the apoptotic signal [ 25 , 26 ] . doi = 10.1007/978-3-662-44006-3_9 id = cord-017640-i8h48ny6 author = Fouqué, Amélie title = The CD95/CD95L Signaling Pathway: A Role in Carcinogenesis date = 2020-01-03 keywords = CD95; FADD; Fas; TNF; cell; signal summary = The intrinsic pathway stems from accumulation of DNA damage, deregulation of mitochondrial function, or virus infection and induces the release of proapoptotic factors from the mitochondria, whereas extrinsic signals are transmitted by the binding of apoptotic ligands to death receptors present at the cell surface. During interactions with respective ligands, members of the death receptor superfamily recruit adaptor proteins such as Fas-associated protein with a death domain (FADD) [7, 8] or tumor necrosis factor (TNF) receptor 1-associated death domain protein (TRADD) [9] , resulting in the aggregation and activation of the initiators caspase-8 and caspase-10 to form the death-inducing signaling complex (DISC) [10] . These type I transmembrane proteins share common features, such as extracellular amino-terminal cysteine-rich domains (CRDs) [19, 20] , which contribute to ligand specificity [21] , and pre-association of the receptor at the plasma membrane [22] [23] [24] and a conserved 80-amino acid sequence located in their cytoplasmic tail called death domain (DD), which is necessary for DISC formation and initiation of the apoptotic signal [25, 26] . doi = 10.1007/978-3-030-30845-2_11 id = cord-002119-kl431ev6 author = Garcia, Elisa title = Cytokine and Growth Factor Activation In Vivo and In Vitro after Spinal Cord Injury date = 2016-06-23 keywords = CNS; IL-1; IL-6; SCI; TNF; cord; injury; spinal summary = Specific inflammatory cytokines such as TNF , IL-1, and IL-6 are synthetized by various cells in the CNS and are known as mediators of the peripheral immune response 8 [118, 192] IL-4 (i) High levels 24 h AI, concentrations remain during 7 days and decrease 3 days AI (i) Neuroinflammatory regulation in various pathological conditions (ii) Confers regenerative properties to macrophages (iii) Controls free radical production in peripheral macrophages and microglia [166, [193] [194] [195] [196] [197] [198] [199] IL-13 (i) Detected 1 day AI (i) Macrophage activation onto M2 phenotype [166, 199] IP-10/CXCL10 (i) Expressed locally 30 [200, [205] [206] [207] Mediators of Inflammation 9 [200, [205] [206] [207] MCP1/CCL2 (i) Detected from 1 h AI with PL at 24 h and remains low up to 24 days AI (i) Macrophage and PMN infiltration mediator [106, 184, 200, 205, 206] min: minutes; AI: after injury; PL: peak levels. doi = 10.1155/2016/9476020 id = cord-295745-iw3ftw3h author = Gershoni, Jonathan M title = Molecular decoys: antidotes, therapeutics and immunomodulators date = 2008-11-18 keywords = TNF; cell; decoy; receptor; toxin summary = Decoys not only provide the means to fine tune the regulation of these phenomena; they also serve as potential leads for the development of recombinant anti-toxins, anti-viral agents and novel therapeutics for combating cancer and inflammatory disease. For almost every membrane receptor of cytokines, growth factors and cell adhesins, soluble versions were found to be naturally produced by cells; hence ''natural decoys'' that function as modifiers of the potent stimulants and regulators of inflammation and immune response. Telovamer, a soluble, high molecular weight anionic polymer represents a ''functional decoy'' able to bind and neutralize both Toxin A and Toxin B of Clostridium difficile yet is not derived from the natural receptor for these toxins. Nature produces such soluble receptors in order to crucially regulate immune responses towards cancer and infection as well as inflammation in general (Figure 1 ). This is particularly relevant for chemokine receptors whose decoys persist as membrane proteins that are effective in ligand binding but ''handicapped'' in signal transduction. doi = 10.1016/j.copbio.2008.10.001 id = cord-278339-6ddsj014 author = Gianfrancesco, Milena title = Characteristics associated with hospitalisation for COVID-19 in people with rheumatic disease: data from the COVID-19 Global Rheumatology Alliance physician-reported registry date = 2020-05-29 keywords = COVID-19; TNF; disease summary = The independent associations between demographic and disease-specific features with the odds of COVID-19 hospitalisation were estimated using multivariable-adjusted logistic regression and reported as OR and 95% CIs; covariates included in the model were age group (<65 years vs >65 years), sex, rheumatic disease (rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), psoriatic arthritis (PsA), axial spondyloarthritis (axSpA) or other spondyloarthritis, vasculitis and other), key comorbidities (hypertension, lung disease, diabetes, cardiovascular disease and chronic renal insufficiency/end-stage renal disease), smoking status (ever vs never), physician-reported disease activity (remission, minimal/low disease activity, moderate disease activity or severe/high disease activity; or as a binary variable: remission and minimal/low disease activity vs moderate and severe/high disease activity), DMARD type (no DMARD, csDMARD only, b/tsDMARD only, csDMARD and b/tsDMARD combination therapy), non-steroidal anti-inflammatory drugs (NSAID) use (yes vs no) and prednisone-equivalent glucocorticoid use (0 mg/ day, 1-9 mg/day, ≥10 mg/day). doi = 10.1136/annrheumdis-2020-217871 id = cord-275730-650sjwyy author = Gogoi, Himanshu title = The Age of Cyclic Dinucleotide Vaccine Adjuvants date = 2020-08-13 keywords = CD8; CDG; CDN; TNF; sting summary = As therapeutic cancer vaccine adjuvants, CDNs induce potent anti-tumor immunity, including cytotoxic T cells and NK cells activation that achieve durable regression in multiple mouse models of tumors. (STINGel) Synthetic ML-RpRp-SS-CDA in multidomain peptide hydrogel (s.c.) [60] Slow-release of CDN and highly effective in maintaining tumor clearance and rejecting tumor growth and provide durable anti-tumor immunity CDG in YSK05 liposome (s.c.) [61] Activation of antigen-specific CTL activity and restrict murine tumor growth completely ADU-S100 (Synthetic ML-RpRp-SS-CDA) in combination with anti-PD1 or anti-CTLA4 antibody (intratumoral) [62] Low-dosage promotes local STING activation primarily in monocytic cell lineages whereas a high-dose resulted in cellular activation at distal sites A combination of ADU-S100 and α-CPI provide durable immunity even against cold tumors Synthetic RpRp-SS-CDG and ML-RpRp-CDA in PBAE nanoparticles and anti-PD1 antibody (intratumoral) [56] Enhanced shelf-life stability for up to nine months. doi = 10.3390/vaccines8030453 id = cord-295683-eoxxal8v author = Gong, R. title = Hepatocyte growth factor suppresses acute renal inflammation by inhibition of endothelial E-selectin date = 2006-04-01 keywords = GSK3; HGF; TNF summary = This study examined the effect of HGF on endothelial E-selectin expression in acute inflammation induced by tumor necrosis factor (TNF)-α. In vitro, HGF suppressed TNF-α-induced cell surface expression of E-selectin in human umbilical vein endothelial cells (HUVEC) and inhibited E-selectin mediated monocytic adhesion to endothelial monolayers. In addition, selective inhibition of GSK3 activity by lithium suppressed TNF-α-induced E-selectin expression and monocytic adhesion, reminiscent of the action of HGF. [6] [7] [8] [9] [10] In the present study, we found that HGF suppresses monocyte to endothelial adhesion and attenuates acute renal inflammation via inhibition of endothelial E-selectin expression. In our study, HGF was found to suppress endothelial E-selectin expression in cultured HUVEC cells and in vivo in rats injected with TNF-a. In summary, HGF suppresses E-selectin expression in the activated endothelium and thereby attenuates monocyte to endothelial adhesion and alleviates acute inflammation in the kidney. doi = 10.1038/sj.ki.5000246 id = cord-354765-abayh871 author = Graham, R. S. title = Calming the Cytokine Storm - Splenic Ultrasound for Treating Inflammatory Disorders and Potentially COVID-19 date = 2020-07-17 keywords = Fig; IL-6; LPS; TNF; ultrasound summary = Here, we show results from the first in-human trials using non-invasive ultrasound stimulation of the spleen to reduce cytokine release in the context of both an acute response in healthy subjects and a chronic inflammatory condition in rheumatoid arthritis patients. In RA patients, we observed that daily splenic ultrasound stimulation results in reduction of blood-borne transcripts encoding for pro-inflammatory markers IL-1β, IL-8, and NFκB, as well as suppresses pathways involved in IL-6 and TNF production. Our additional pre-clinical animal data further demonstrates that in addition to dampening cytokine output and circulating monocyte invasiveness, prophylactic ultrasound activation of the splenic neuroimmune pathway results in enhanced antibody response upon exposure to an inflammatory antigen. By presenting the first in-human data from two independent studies using different devices and protocols, we have consistently demonstrated that non-invasive ultrasound stimulation of the spleen drives anti-inflammatory effects in the context of both an acute response in healthy subjects and a chronic inflammatory condition. doi = 10.1101/2020.07.14.20153528 id = cord-015910-d9gxew91 author = Grimble, Robert F. title = The Interaction Between Nutrition and Inflammatory Stress Throughout the Life Cycle date = 2005 keywords = GSH; IL-6; TNF; cytokine; effect; inflammatory; production; response; study summary = Binding of the transcription factors is implicated in activation of a wide range of genes associated with inflammation and the immune response, including those encoding cytokines, cytokine receptors, cell adhesion molecules, acute-phase proteins, and growth factors (Schreck, Rieber, & Baeurerle, 1991) (Fig. 4 ) . While inflammation may be exerting deleterious effects most obviously in patients, people on the borderline of health and disease living in the general population Table 4 Nutrients Commonly Used in Immunonutrient Supplements and Their Potential Mode of Action • n-3 polyunsaturated fatty acids: act as anti-inflammatory agents and reverse immunosuppression • Sulfur amino acids and their precursors: enhance antioxidant status via GSH synthesis • Glutamine: nutrient for immune cells, improves gut barrier function, precursor for GSH • Arginine: stimulates nitric oxide and growth hormone production, improves helper T-cell numbers • Nucleotides: RNA and DNA precursors, improve T-cell function may also require nutritional modulation of ongoing inflammatory processes. doi = 10.1385/1-59259-952-4:387 id = cord-017309-pt27efu1 author = Gupta, G. S. title = Selectins and Associated Adhesion Proteins in Inflammatory disorders date = 2012-03-20 keywords = TNF; VCAM-1; adhesion; cell; endothelial; expression; level; patient; selectin summary = Activation of endothelial cells (EC) with different stimuli induces the expression of E-and P-selectins, and other adhesion molecules (ICAM-1, VCAM-1), involved in their interaction with circulating cells. Accordingly, population studies have explored the association of ischaemic heart disease with gene polymorphisms of the inflammatory molecules: tumor necrosis factors (TNF) a and b, transforming growth factors (TGF) b1 and 2, P and E selectins, and platelet endothelial cell adhesion molecule (PECAM) 1. Endothelial dysfunction in type 2 diabetic patients is associated with inflammation, increased levels of circulating soluble adhesion molecules (VCAM-1 and E-selectin), and inducing production of ROS, and urinary albumin excretion (Potenza et al. The A 561 C polymorphism of E-selectin gene may be associated with disease progression in patients with chronic HBV infection and control the expression of plasma soluble levels, while the G 98 T polymorphism may be related to fibrotic severity in Chinese population (Wu et al. doi = 10.1007/978-3-7091-1065-2_44 id = cord-282242-5tkhjiwl author = Gómez-Laguna, J. title = Cytokine Expression by Macrophages in the Lung of Pigs Infected with the Porcine Reproductive and Respiratory Syndrome Virus date = 2009-08-19 keywords = IFN; PRRSV; TNF summary = title: Cytokine Expression by Macrophages in the Lung of Pigs Infected with the Porcine Reproductive and Respiratory Syndrome Virus The aim of the present study was to characterize the production of cytokines by subpopulations of pulmonary macrophages in pigs infected by the PRRS virus (PRRSV). Several studies have examined the role of cytokines in the pathogenesis of PRRS (Van Reeth and Nauwynck, 2000) ; however, it is not clear how cytokines participate in macrophage activation during PRRSV infection or how they regulate development of the immune response to the virus. The expression of IFN-g by macrophages and lymphocytes has been previously reported in the lung of PRRSV-infected pigs (Thanawongnuwech et al., 2003) . Therefore, the expression of IL-10 observed in the present study might be responsible for reduced expression of cytokines such as IFN-a, IFN-g, IL-12p40 and TNF-a, that in turn may impair prolonged viral replication in the lung of infected animals. doi = 10.1016/j.jcpa.2009.07.004 id = cord-023392-axd0901z author = Hansen, T. K. title = Association between Mannose‐Binding Lectin and Vascular Complications in Type 1 Diabetes date = 2008-06-28 keywords = CD8; IFN; IL-12; MBL; TNF; cell summary = We demonstrate that Cw6 þ psoriasis patients had significant CD8 þ T-cell IFN-g responses to peptides from K17 and M6 protein selected on the basis of sequence homology and predicted HLA-Cw*0602 binding. The uptake of MBP by B cells and the presentation of MBP-derive peptides to T helper (Th) cells by B cells may be promoted by the formation of complement (C) activating immune complexes (ICs) between MBP and natural autoantibodies in healthy individuals and disease-associated anti-MBP antibodies in MS patients, respectively. While MBP did not induce measurable proliferation of B cells nor CD4 þ T cells, we observed the production of TNF-a, IFN-g and IL-10 by PBMC in response to incubation with MBP in the presence of sera from healthy controls as well as sera from MS patients. In conclusion, the results of this study suggest an involvement of the ASMase in the activation, expansion or maturation of virus-specific CD8 þ T cells during the acute infection of mice with the LCM virus. doi = 10.1111/j.0300-9475.2004.01423i.x id = cord-344204-qq2vqzc2 author = Hariharan, Apurva title = The Role and Therapeutic Potential of NF-kappa-B Pathway in Severe COVID-19 Patients date = 2020-11-07 keywords = COVID-19; SARS; TNF summary = Severe presentations of COVID-19 such as severe pneumonia and acute respiratory distress syndrome (ARDS) have been associated with the post-viral activation and release of cytokine/chemokines which leads to a "cytokine storm" causing inflammatory response and destruction, mainly affecting the lungs. Immunomodulation at the level of NF-κB activation and inhibitors of NF-κB (IκB) degradation along with TNF-α inhibition will potentially result in a reduction in the cytokine storm and alleviate the severity of COVID-19. During previous coronavirus outbreaks, such as SARS-CoV and the Middle East Respiratory syndrome coronavirus (MERS-CoV) , it was reported that viral proteins such as nsp1, nsp3a, nsp7a, spike, and nucleocapsid protein all caused excessive NF-κB activation, possibly contributing to severe disease and high case-fatality rate (DeDiego et al. Herein, we review current literature on the effect of SARS-nCoV-2 infection on NF-κB activation and discuss the potential therapeutic role of inhibitors of this pathway in the treatment of COVID-19. doi = 10.1007/s10787-020-00773-9 id = cord-001039-qocuprwb author = Hayasaka, Daisuke title = TNF-α Acts as an Immunoregulator in the Mouse Brain by Reducing the Incidence of Severe Disease Following Japanese Encephalitis Virus Infection date = 2013-08-05 keywords = IL-10; JEV; TNF; figure summary = We next compared severe or mild cases of mice infected with JEV exhibiting doseindependent mortality and investigated the specific host responses such as TNF-α and IL-10 expression in the CNS. Corresponding to the viral loads, histopathological examination showed that a large number of neurons displayed JEV antigens and severe cuffing was observed in the brain cortex of JaTH160-infected mice at 9 day pi ( Figure 1F ). Following inoculation with JaOArS982 virus, there were no significant differences of infectious viral loads in the brain cortex between WT, IL-10 KO and TNF-α KO at 5, 9 and 11 days pi ( Figure 5B ). TNF-α KO mice exhibited significantly increased levels of IFN-γ and IL-5 in the brains compared with WT and/or IL-10 KO mice at 5 and 7 days pi following JaTH160 inoculation ( Figure 7C and D) . doi = 10.1371/journal.pone.0071643 id = cord-322250-7kjakuyw author = He, Jia title = Anemoside B4 protects against Klebsiella pneumoniae- and influenza virus FM1-induced pneumonia via the TLR4/Myd88 signaling pathway in mice date = 2020-07-02 keywords = Fig; IL-6; TLR4; TNF summary = title: Anemoside B4 protects against Klebsiella pneumoniaeand influenza virus FM1-induced pneumonia via the TLR4/Myd88 signaling pathway in mice This study aims to investigate that anemoside B4 attenuates the inflammatory responses in Klebsiella pneumonia (KP)and influenza virus FM1 (FM1)-induced pneumonia mice model. The counts of neutrophil (NEU) and white blood cell (WBC), the level of myeloperoxidase (MPO), and the release of pro-inflammatory cytokines TNF-α, IL-1β, and IL-6 increased by KP or FM1 infection, which were reversed by anemoside B4. In addition, significant increase was observed in the TNF-α (Fig. 3d, g) , IL-6 ( Fig. 3e, h) , IL-1β (Fig. 3f ) , and MPO (Fig. 3i) in the BALF and lung tissue samples collected from the KP-infected pneumonia mice, which were reversed by anemoside B4. Influenza virus FM1-infected pneumonia leads to an inflammatory storm, suggesting that many pro-inflammatory cytokines like TNF-α and IL-6 released into blood and lung tissue [28] [29] [30] . doi = 10.1186/s13020-020-00350-w id = cord-023439-r04y1j22 author = Hedegaard, C. J. title = The Role of Immune Complexes Consisting of Myelin Basic Protein (MBP), Anti‐MBP Antibodies and Complement in Promoting CD4(+) T‐cell Responses to MBP in Health and Multiple Sclerosis date = 2008-06-28 keywords = CD8; IFN; MBL; MBP; TNF; cell summary = We demonstrate that Cw6 þ psoriasis patients had significant CD8 þ T-cell IFN-g responses to peptides from K17 and M6 protein selected on the basis of sequence homology and predicted HLA-Cw*0602 binding. The uptake of MBP by B cells and the presentation of MBP-derive peptides to T helper (Th) cells by B cells may be promoted by the formation of complement (C) activating immune complexes (ICs) between MBP and natural autoantibodies in healthy individuals and disease-associated anti-MBP antibodies in MS patients, respectively. While MBP did not induce measurable proliferation of B cells nor CD4 þ T cells, we observed the production of TNF-a, IFN-g and IL-10 by PBMC in response to incubation with MBP in the presence of sera from healthy controls as well as sera from MS patients. doi = 10.1111/j.0300-9475.2004.01423k.x id = cord-347298-7kqrl3rv author = Hedger, M.P. title = Immunology of the Testis and Male Reproductive Tract date = 2010-07-12 keywords = Hedger; IFN; IL1; Leydig; MHC; Sertoli; TNF; cell; testis summary = Thus, it appears unlikely that a lack of APCs is a contributing factor in testicular immune privilege, although differences in the number and distribution of MHC class II-expressing cells in the interstitial tissue of different species or strains may help to explain differences in susceptibility to autoimmune orchitis (Flickinger et al. Moreover, while inhibition of Leydig cell steroidogenesis during inflammation may involve indirect effects at the level of the pituitary, or the actions of inflammatory mediators produced by the testicular macrophages and Sertoli cells, there is evidence that these cells can also respond directly to TLR ligands (Bhushan et al. Activation of p38/Jnk is implicated in the stimulation of proliferation by immature Sertoli cells and the regulation of blood-testis barrier dynamics, steroidogenesis, and multiple inflammatory responses, including the production of IL6, iNOS, monocyte chemoattractant protein 1, and leukocyte adhesion molecules, in the mature Sertoli cell (De Cesaris et al. doi = 10.1016/b978-0-08-046884-6.01112-x id = cord-335185-3qi29i6n author = Hendry, Bruce M. title = Hypothesis: Pentoxifylline is a potential cytokine modulator therapeutic in COVID‐19 patients date = 2020-07-26 keywords = COVID-19; Pentoxifylline; TNF summary = doi = 10.1002/prp2.631 id = cord-023388-btbf6wkg author = Hoffmann, H. J. title = Decrease in Fine T‐cell Subset ratio MT2/MT1 During Steroid Reduction of Asthmatic Patients date = 2008-06-28 keywords = CD8; IFN; IL-12; MBL; TNF; cell summary = We demonstrate that Cw6 þ psoriasis patients had significant CD8 þ T-cell IFN-g responses to peptides from K17 and M6 protein selected on the basis of sequence homology and predicted HLA-Cw*0602 binding. The uptake of MBP by B cells and the presentation of MBP-derive peptides to T helper (Th) cells by B cells may be promoted by the formation of complement (C) activating immune complexes (ICs) between MBP and natural autoantibodies in healthy individuals and disease-associated anti-MBP antibodies in MS patients, respectively. While MBP did not induce measurable proliferation of B cells nor CD4 þ T cells, we observed the production of TNF-a, IFN-g and IL-10 by PBMC in response to incubation with MBP in the presence of sera from healthy controls as well as sera from MS patients. In conclusion, the results of this study suggest an involvement of the ASMase in the activation, expansion or maturation of virus-specific CD8 þ T cells during the acute infection of mice with the LCM virus. doi = 10.1111/j.0300-9475.2004.01423ah.x id = cord-297128-s5c9h4lm author = Hong, Joung-Woo title = Anti-inflammatory activity of cinnamon water extract in vivo and in vitro LPS-induced models date = 2012-11-28 keywords = CWE; LPS; TNF summary = title: Anti-inflammatory activity of cinnamon water extract in vivo and in vitro LPS-induced models The goal of this study is to investigate the in vivo and in vitro inhibitory effect of cinnamon water extract (CWE) on lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF)-α and its underlying intracellular mechanisms. Inhibitory effect of the CWE fraction containing highmolecular-weight compounds on signaling molecules in LPS-stimulated macrophages In addition, LPS-induced IκBα degradation and MAP kinase phosphorylation in macrophages was strongly inhibited by the polyphenol-rich CWE fraction. Oral administration of CWE decreased serum levels of LPS-induced TNF-α and IL-6, but such anti-inflammatory activity was attenuated in the high dose group. The inhibitory effect of CWE on the signaling pathways mediated by NF-κB and MAP kinases occurred in its polyphenol-rich high MW fraction. CWE inhibited IκBα degradation and MAP kinase activation in LPS-stimulated macrophages in vitro. Anti-inflammatory activity of cinnamon water extract in vivo and in vitro LPS-induced models doi = 10.1186/1472-6882-12-237 id = cord-306577-gq6fss5l author = Hsueh, Wei title = Neonatal Necrotizing Enterocolitis: Clinical Considerations and Pathogenetic Concepts date = 2002-11-11 keywords = LPS; NEC; PAF; TNF; platelet summary = Injection of PAF induces intestinal necrosis, and PAF antagonists prevent the bowel injury induced by bacterial endotoxin, hypoxia, or challenge with tumor necrosis factor-a (TNF) plus endotoxin in adult rats. The initial event in our experimental models of NEC is probably polymorphonuclear leukocyte (PMN) activation and adhesion to venules in the intestine, which initiates a local inflammatory reaction involving proinflammatory mediators including TNF, complement, prostaglandins, and leukotriene C4. We developed a model of bowel necrosis in adult rats and mice by injecting endotoxin (lipopolysaccharide, LPS) [32] , PAF (platelet-activating factor, paf-acether) [33, 34] , tumor necrosis factor-␣ (TNF) [35] , or a combination of these agents. Experimental evidence strongly supports the role of PAF, LPS, and TNF in acute ischemic bowel necrosis and in the neonatal rat model of NEC. Hypoxia causes ischemic bowel necrosis in rats: the role of platelet-activating factor (PAF-acether) doi = 10.1007/s10024-002-0602-z id = cord-023407-s85g7g0x author = Huang, Y.‐M. title = Anti‐Inflammatory Liver X Receptors and Related Molecules in Multiple Sclerosis Patients from Sardinia and Sweden date = 2008-06-28 keywords = CD8; IFN; IL-12; MBL; TNF; cell summary = We demonstrate that Cw6 þ psoriasis patients had significant CD8 þ T-cell IFN-g responses to peptides from K17 and M6 protein selected on the basis of sequence homology and predicted HLA-Cw*0602 binding. The uptake of MBP by B cells and the presentation of MBP-derive peptides to T helper (Th) cells by B cells may be promoted by the formation of complement (C) activating immune complexes (ICs) between MBP and natural autoantibodies in healthy individuals and disease-associated anti-MBP antibodies in MS patients, respectively. While MBP did not induce measurable proliferation of B cells nor CD4 þ T cells, we observed the production of TNF-a, IFN-g and IL-10 by PBMC in response to incubation with MBP in the presence of sera from healthy controls as well as sera from MS patients. In conclusion, the results of this study suggest an involvement of the ASMase in the activation, expansion or maturation of virus-specific CD8 þ T cells during the acute infection of mice with the LCM virus. doi = 10.1111/j.0300-9475.2004.01423d.x id = cord-017520-r786yd6i author = Huber-Lang, Markus title = Inflammatory Changes and Coagulopathy in Multiply Injured Patients date = 2015-05-14 keywords = IL-6; TNF; cell; inflammatory; trauma summary = Severe tissue trauma leads to an early activation of several danger recognition systems, including the complement and the coagulation system, often resulting in an overwhelming almost synchronic proand anti-inflammatory response of the host. Although the immune response is associated with beneficial effects at the site of injury including the elimination of exogenous and endogenous danger molecules as well as the initiation of regenerative processes, an exaggerated systemic inflammatory response significantly contributes to posttraumatic complications such as multiple organ failure (MOF) and early death. The steps of an inflammatory reaction to trauma involve fluid phase mediators (cytokines, chemokines, coagulation-and complement activation products, oxygen radicals, eicosanoids, and nitric oxide (NO)) and cellular effectors (neutrophils, monocytes/macrophages, and endothelial cells) that translate the trauma-induced signals into cellular responses. doi = 10.1007/978-3-662-47212-5_4 id = cord-023387-tyeh14wz author = Hvas, C. L. title = Probiotic Bacteria Induce Regulatory Cytokine Production via Dendritic Cells date = 2008-06-28 keywords = CD8; IFN; IL-12; MBL; TNF; cell; lactobacillus summary = We demonstrate that Cw6 þ psoriasis patients had significant CD8 þ T-cell IFN-g responses to peptides from K17 and M6 protein selected on the basis of sequence homology and predicted HLA-Cw*0602 binding. The uptake of MBP by B cells and the presentation of MBP-derive peptides to T helper (Th) cells by B cells may be promoted by the formation of complement (C) activating immune complexes (ICs) between MBP and natural autoantibodies in healthy individuals and disease-associated anti-MBP antibodies in MS patients, respectively. While MBP did not induce measurable proliferation of B cells nor CD4 þ T cells, we observed the production of TNF-a, IFN-g and IL-10 by PBMC in response to incubation with MBP in the presence of sera from healthy controls as well as sera from MS patients. In conclusion, the results of this study suggest an involvement of the ASMase in the activation, expansion or maturation of virus-specific CD8 þ T cells during the acute infection of mice with the LCM virus. doi = 10.1111/j.0300-9475.2004.01423au.x id = cord-348855-lnltoj1n author = Iannaccone, Giulia title = Weathering the Cytokine Storm in COVID-19: Therapeutic Implications date = 2020-06-29 keywords = COVID-19; SARS; TNF; patient summary = doi = 10.1159/000509483 id = cord-023394-ptfjxpo6 author = Isa, A. title = Mapping of the Ex Vivo Cellular Immune Response Against the Complete Human Parvovirus B19 Genome During Acute Infection date = 2008-06-28 keywords = CD8; IFN; IL-12; MBL; TNF; cell summary = We demonstrate that Cw6 þ psoriasis patients had significant CD8 þ T-cell IFN-g responses to peptides from K17 and M6 protein selected on the basis of sequence homology and predicted HLA-Cw*0602 binding. The uptake of MBP by B cells and the presentation of MBP-derive peptides to T helper (Th) cells by B cells may be promoted by the formation of complement (C) activating immune complexes (ICs) between MBP and natural autoantibodies in healthy individuals and disease-associated anti-MBP antibodies in MS patients, respectively. While MBP did not induce measurable proliferation of B cells nor CD4 þ T cells, we observed the production of TNF-a, IFN-g and IL-10 by PBMC in response to incubation with MBP in the presence of sera from healthy controls as well as sera from MS patients. In conclusion, the results of this study suggest an involvement of the ASMase in the activation, expansion or maturation of virus-specific CD8 þ T cells during the acute infection of mice with the LCM virus. doi = 10.1111/j.0300-9475.2004.01423n.x id = cord-259367-2e998to9 author = Jacques, Alexandre title = Macrophage interleukin-6 and tumour necrosis factor-α are induced by coronavirus fixation to Toll-like receptor 2/heparan sulphate receptors but not carcinoembryonic cell adhesion antigen 1a date = 2009-09-01 keywords = C57BL/6; IL-6; TNF summary = In this study, we demonstrate that the pro-inflammatory cytokines IL-6 and TNF-a, produced by MHV3-infected peritoneal macrophages, were induced by the fixation of protein S of MHV3 on TLR2 associated with regions enriched in heparan sulphate instead of CEA-CAM1a. 23, 44 To determine whether that the pro-inflammatory cytokines induced by L2-MHV3 in macrophages depend on viral fixation to regions enriched in heparan sulphate, resident peritoneal macrophages from C57BL/6 and Ceacam1a )/) mice were treated in vitro with heparin and infected further with L2-MHV3. To identify the intracellular signalling pathways involved in the TLR2/heparan sulphate region-dependent production of IL-6 and TNF-a, peritoneal macrophages from C57BL/6 and Ceacam1a )/) mice were treated with p38 (SB203580) and ERK-1/2 (U0126) MAPK inhibitors and infected in vitro with L2-MHV3. 21, 48, 49 However, we have demonstrated that viral fixation to the CEACAM1a receptor is not directly involved in the secretion of IL-6 and TNF-a by MHV3-infected peritoneal macrophages as these cytokines were also induced in cells from Ceacam1a )/) mice and regulated by the MAPK pathways. doi = 10.1111/j.1365-2567.2008.02946.x id = cord-022526-j9kg00qf author = Jones, Samuel L. title = Disorders of the Gastrointestinal System date = 2009-05-18 keywords = NSAID; Salmonella; TNF; cause; cell; clinical; clostridium; colon; diarrhea; disease; dpj; effect; equine; esophageal; figure; fluid; gastric; horse; increase; inflammatory; intestinal; large; occur; result; sign; small; treatment summary = Examination of the cardiovascular system (heart, peripheral pulse, and mucous membranes), lungs, and abdomen is essential to detect clinical signs of systemic inflammation from endotoxemia, coagulation disorders, dehydration, ileus, shock, and other abnormalities resulting from injury to the small or large intestine. Several reports suggest the efficacy of cisapride in managing intestinal disease in horses, including the resolution of persistent large colon impaction, treatment of equine grass sickness, and as a preventative for POI in horses after small intestinal surgery (0.1 mg/kg body mass intramuscularly during the postoperative period). 9 Primary role-players in DPJ-associated ileus include peritoneal inflammation, inflammatory cell migration/activation within the muscularis, small intestinal mechanical distention, and effects of endotoxin absorption. Diarrhea probably results from the severe ulceration and inflammation of the large intestine, causing increased secretion of water, electrolytes, and protein and decreased absorption of fluid. doi = 10.1016/b0-72-169777-1/50015-9 id = cord-022631-s4n24xij author = Jonsson, M. V. title = Germinal Centres in Primary Sjögren''s Syndrome Indicate a Certain Clinical Immunological Phenotype date = 2008-06-28 keywords = CD8; IFN; IL-12; MBL; TNF; cell summary = We demonstrate that Cw6 þ psoriasis patients had significant CD8 þ T-cell IFN-g responses to peptides from K17 and M6 protein selected on the basis of sequence homology and predicted HLA-Cw*0602 binding. The uptake of MBP by B cells and the presentation of MBP-derive peptides to T helper (Th) cells by B cells may be promoted by the formation of complement (C) activating immune complexes (ICs) between MBP and natural autoantibodies in healthy individuals and disease-associated anti-MBP antibodies in MS patients, respectively. While MBP did not induce measurable proliferation of B cells nor CD4 þ T cells, we observed the production of TNF-a, IFN-g and IL-10 by PBMC in response to incubation with MBP in the presence of sera from healthy controls as well as sera from MS patients. In conclusion, the results of this study suggest an involvement of the ASMase in the activation, expansion or maturation of virus-specific CD8 þ T cells during the acute infection of mice with the LCM virus. doi = 10.1111/j.0300-9475.2004.01423h.x id = cord-003686-1pfk4qve author = Kaneko, Naoe title = The role of interleukin-1 in general pathology date = 2019-06-06 keywords = IL-1; IL-1R1; NLRP3; TNF; cell; disease; patient summary = The majority of NOD-like receptors such as NLRP1, NLRP3, NLRC4, NLRP6, and NLRP12 can interact with apoptosis-associated speck-like protein containing a caspase-recruitment domain (ASC) and caspase-1, and the resulting complex is a sensor of cell injury called "inflammasome", an interleukin (IL)-1β-processing platform that plays a crucial role in IL-1β maturation and secretion from cells. NLRP3 inflammasomes have also been reported to be involved in low-grade subclinical inflammation induced by chronic exposure to high levels of free fatty acids and glucose, leading to increased apoptosis and impaired insulin secretion of β-cells in obese type 2 diabetes mellitus (T2D) patients [102] [103] [104] . Canakinumab and anakinra were also effective for patients with Schnitzler syndrome, an adult-onset autoinflammatory disease characterized by focal urticaria and systemic inflammation including fever with bone and muscle pain, in the first placebo-controlled study, and several clinical trials are currently ongoing [186] [187] [188] [189] . doi = 10.1186/s41232-019-0101-5 id = cord-023415-hhvmsn5b author = Karlsson, H. title = Pattern of Cytokine Responses to Gram‐Positive and Gram‐Negative Commensal Bacteria is Profoundly Changed when Monocytes Differentiate into Dendritic Cells date = 2008-06-28 keywords = CD8; IFN; IL-12; MBL; TNF; cell summary = We demonstrate that Cw6 þ psoriasis patients had significant CD8 þ T-cell IFN-g responses to peptides from K17 and M6 protein selected on the basis of sequence homology and predicted HLA-Cw*0602 binding. The uptake of MBP by B cells and the presentation of MBP-derive peptides to T helper (Th) cells by B cells may be promoted by the formation of complement (C) activating immune complexes (ICs) between MBP and natural autoantibodies in healthy individuals and disease-associated anti-MBP antibodies in MS patients, respectively. While MBP did not induce measurable proliferation of B cells nor CD4 þ T cells, we observed the production of TNF-a, IFN-g and IL-10 by PBMC in response to incubation with MBP in the presence of sera from healthy controls as well as sera from MS patients. In conclusion, the results of this study suggest an involvement of the ASMase in the activation, expansion or maturation of virus-specific CD8 þ T cells during the acute infection of mice with the LCM virus. doi = 10.1111/j.0300-9475.2004.01423at.x id = cord-262511-96xp1v0r author = Khabar, Khalid S. A. title = Rapid transit in the immune cells: the role of mRNA turnover regulation date = 2007-03-30 keywords = MAPK; RNA; TNF-; TTP summary = Post-transcriptional regulation contributes significantly to this rapid transit by several mechanisms, including mRNA stability modulation and translational control; collectively, they aim to control the expression of key gene products involved in the immune response. The stabilization of cytokine mRNA and other immune response gene products can occur by the activity of mRNA stabilization-promoting proteins such as human antigen (HuR) protein or by inactivation of RNA decay-promoting proteins such as the zinc finger protein, tristetraprolin (TTP). Traditionally, post-transcriptional regulation in innate immunity has been studied in response to the bacterial endotoxin, LPS, which binds CD14 in a complex with TLR4 on the surface of neutrophils and macrophages and initiates a cascade of signals that causes cell activation, the inflammatory response, and phagocytosis [35] . With the coordinated kinetics model, stabilizing RNA-binding proteins such as HuR can occur initially following immune cell activation, allowing rapid and early response of cytokine production. doi = 10.1189/jlb.0207109 id = cord-252725-e3pazjdi author = Khalil, Ayman title = The upshot of Polyphenolic compounds on immunity amid COVID-19 pandemic and other emerging communicable diseases: An appraisal date = 2020-10-15 keywords = COVID-19; Fig; SARS; TNF; anti; virus summary = In fact, several studies and clinical trials increasingly proved the role of polyphenols in controlling numerous human pathogens including SARS and MERS, which are quite similar to COVID-19 through the enhancement of host immune response against viral infections by different biological mechanisms. Actually, data indicated that activation of the nuclear factor (NF)-κB transcription factor (NF-κB) signaling pathway represents a major contribution to the inflammation induced post SARS-CoV infection and that NF-κB inhibitors are promising antiviral drugs against infections caused by the virus and potentially other pathogenic human coronaviruses [8] . Moreover, it was found to reduce the reactive oxygenated species (ROS) produced during viral infection and subsequently decrease pro-inflammatory markers such as IL-8, TNF-α, IL-1β and IL-6 [25] and increases anti-inflammatory cytokines such as IL-10 [35] , indicating that it has clear antiviral effects on several respiratory and common cold viruses through its ability to reduce virus imputation, replication and viral load in vitro, as well as lung inflammation and airways hyper-responsiveness in vivo [29] . doi = 10.1007/s13659-020-00271-z id = cord-300991-ipy24zxp author = Khan, Amira Sayed title = Obesity and COVID-19: Oro-Naso-Sensory Perception date = 2020-07-08 keywords = SARS; TNF; covid-19; obesity; olfactory summary = Through a recent upsurge of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic, the clinical assessment of most of the coronavirus disease 19 (COVID-19) patients clearly presents a health condition with the loss of oro-naso-sensory (ONS) perception, responsible for the detection of flavor and savor. Hence, obesity represents a great risk factor for SARS-CoV-2 infection, as it may hide the viral-associated altered ONS symptoms, thus leading to a high mortality rate in these subjects. Moreover, the number of immunosuppressive T-regulatory, Treg (CD4 + CD25 + Foxp3 + ) cells and concentrations of IL-6, IL-10, and C-reactive protein (CRP) were upregulated in patients with severe COVID-19 [18] , suggesting that SARS-CoV-2 infection may lead to "over-immunosuppression" in the case of obesity ( Figure 1 ). SARS-CoV-2 infection may further aggravate the ONS functions; mask the obesity-induced inflammation, including loss of taste and smell; and render the obese subjects more vulnerable and prone to severe pathophysiological consequences such as RTI, leading to death. doi = 10.3390/jcm9072158 id = cord-003013-h8txbd3p author = Kim, Sena title = Differential Regulation of Toll-Like Receptor-Mediated Cytokine Production by Unfolded Protein Response date = 2018-04-24 keywords = TLR; TNF summary = Under ER stress, unfolded protein response (UPR) signaling pathways participate in upregulating inflammatory cytokine production via NF-kappaB, MAPK, and GSK-3β. Toll-like receptor (TLRs) can recognize pathogenassociated molecular patterns (PAMPs) and dangerassociated molecular patterns (DAMPs) and induce TLRmediated intracellular signaling cascades to eliminate the pathogens through the production of proinflammatory cytokines including TNF-α, IL-6, IL-1β, and IL-8, but its uncontrolled activation can damage the host [9] . ER stress has been shown to regulate proinflammatory cytokine production, which are mediated by TLR signaling cascade components such as NF-kappaB, MAPK, and GSK-3β. In addition, ER stress shares TLR-mediated signaling components with pro-and anti-inflammatory cytokine productions, leading to the activation of NF-kappaB and MAPKs. The XBP1 deletion or chemical chaperone treatment in macrophages alleviates proinflammatory cytokine production by LPS. Toll-like receptor-mediated activation of intracellular signaling pathways results in increased production of proinflammatory cytokines including TNF-α, IL-6, and IL-1β. Endoplasmic reticulum stress-induced IRE1α activation mediates cross-talk of GSK-3β and XBP-1 to regulate inflammatory cytokine production doi = 10.1155/2018/9827312 id = cord-267270-r17z4d8x author = Kipar, A. title = Age-related dynamics of constitutive cytokine transcription levels of feline monocytes date = 2005-01-18 keywords = IL-6; TNF summary = However, in order to characterize the effect of age, feline monocyte functions were examined for changes in cytokine transcription levels in early stages of immunosenescence. For this purpose, isolated, short-term cultured monocytes from barrier-maintained adult cats of different ages (15 mo to 10 yr) were examined for transcription of IL-1β, IL-6, IL-10, IL-12 p40 and TNF-α by real-time PCR. One previous study actually showed significantly increased constitutive production of IL-1b and IL-6 in circulating monocytes of older female compared to young adult female human individuals, whereas no changes in the constitutive TNF-a production were observed (Sadeghi et al., 1999) . It seems plausible that despite increased or similar constitutive cytokine transcription, monocytes of older cats might exhibit an impaired reactive activation after virus infection (Kipar et al., 2005) . doi = 10.1016/j.exger.2004.12.007 id = cord-023410-eblcf902 author = Kollgaard, T. M. title = Clonally Expanded CD8(+) T cells in Allogeneic Bone Marrow Transplantation date = 2008-06-28 keywords = CD8; IFN; IL-12; MBL; TNF; cell summary = We demonstrate that Cw6 þ psoriasis patients had significant CD8 þ T-cell IFN-g responses to peptides from K17 and M6 protein selected on the basis of sequence homology and predicted HLA-Cw*0602 binding. The uptake of MBP by B cells and the presentation of MBP-derive peptides to T helper (Th) cells by B cells may be promoted by the formation of complement (C) activating immune complexes (ICs) between MBP and natural autoantibodies in healthy individuals and disease-associated anti-MBP antibodies in MS patients, respectively. While MBP did not induce measurable proliferation of B cells nor CD4 þ T cells, we observed the production of TNF-a, IFN-g and IL-10 by PBMC in response to incubation with MBP in the presence of sera from healthy controls as well as sera from MS patients. In conclusion, the results of this study suggest an involvement of the ASMase in the activation, expansion or maturation of virus-specific CD8 þ T cells during the acute infection of mice with the LCM virus. doi = 10.1111/j.0300-9475.2004.01423bm.x id = cord-023393-8nye3nc8 author = Krarup, A. title = Mannan‐Binding Lectin, L‐Ficolin and H‐Ficolin Selectively Binds to Different Bacteria date = 2008-06-28 keywords = CD8; IFN; IL-12; MBL; TNF; cell summary = We demonstrate that Cw6 þ psoriasis patients had significant CD8 þ T-cell IFN-g responses to peptides from K17 and M6 protein selected on the basis of sequence homology and predicted HLA-Cw*0602 binding. The uptake of MBP by B cells and the presentation of MBP-derive peptides to T helper (Th) cells by B cells may be promoted by the formation of complement (C) activating immune complexes (ICs) between MBP and natural autoantibodies in healthy individuals and disease-associated anti-MBP antibodies in MS patients, respectively. While MBP did not induce measurable proliferation of B cells nor CD4 þ T cells, we observed the production of TNF-a, IFN-g and IL-10 by PBMC in response to incubation with MBP in the presence of sera from healthy controls as well as sera from MS patients. In conclusion, the results of this study suggest an involvement of the ASMase in the activation, expansion or maturation of virus-specific CD8 þ T cells during the acute infection of mice with the LCM virus. doi = 10.1111/j.0300-9475.2004.01423al.x id = cord-023438-g0k0vvdc author = Krog, J. title = The Effects of Hyperbaric Exposure on Human Peripheral Blood Mononuclear Cells, with Special Emphasis on Natural Killer Cell Cytotoxicity and Subsets date = 2008-06-28 keywords = CD8; IFN; IL-12; MBL; TNF; cell summary = We demonstrate that Cw6 þ psoriasis patients had significant CD8 þ T-cell IFN-g responses to peptides from K17 and M6 protein selected on the basis of sequence homology and predicted HLA-Cw*0602 binding. The uptake of MBP by B cells and the presentation of MBP-derive peptides to T helper (Th) cells by B cells may be promoted by the formation of complement (C) activating immune complexes (ICs) between MBP and natural autoantibodies in healthy individuals and disease-associated anti-MBP antibodies in MS patients, respectively. While MBP did not induce measurable proliferation of B cells nor CD4 þ T cells, we observed the production of TNF-a, IFN-g and IL-10 by PBMC in response to incubation with MBP in the presence of sera from healthy controls as well as sera from MS patients. In conclusion, the results of this study suggest an involvement of the ASMase in the activation, expansion or maturation of virus-specific CD8 þ T cells during the acute infection of mice with the LCM virus. doi = 10.1111/j.0300-9475.2004.01423aa.x id = cord-301946-erzh30mt author = Kwak-Kim, Joanne title = COVID-19 and immunomodulation treatment for women with reproductive failures date = 2020-06-12 keywords = COVID-19; RFI; SARS; TNF summary = With the Coronavirus Disease 2019 (COVID-19) pandemic, patient care has been significantly challenged not only for the COVID-19 cases but for the others, including pregnant women with a history of reproductive failures (RF), such as recurrent pregnancy losses (RPL), repeated implantation failures (RIF), with immune etiologies including autoimmune diseases, cellular immune dysfunction, and rheumatic conditions. SARS-CoV (Severe Acute Respiratory Syndrome Coronavirus), which caused the SARS outbreak in 2003, infects macrophages and T cells (Perlman and Dandekar 2005) and induces various cytokines, such as type I IFN, TNF-α, IL-1, etc., and B cell-related antibodies (Prompetchara et al. With the currently available data, it is unlikely that the use of IVIg in patients with RFI will impact the chances of contracting the disease or negatively affect the clinical course in women with COVID-19 infection during pregnancy. doi = 10.1016/j.jri.2020.103168 id = cord-002209-xs6qigg4 author = Kıray, Hülya title = The multifaceted role of astrocytes in regulating myelination date = 2016-09-17 keywords = CNS; CNTF; TNF; astrocyte summary = In experimental allergic encephalomyelitis (EAE), a widely used animal model of MS, where demyelination is induced by myelin antigens, administered together with adjuvant that contains bacterial components (Traugott and Lebon, 1988; Tsukada et al., 1991; Villarroya et al., 1996) , GFAP expression was seen on more numerous and much larger astrocytic processes in chronic lesions compared to normal appearing white matter (Webster et al., 1985; Eng et al., 1971) . The milder "activated" astrocytes can secrete a range of factors including; neurotrophic factors, growth factors, and cytokines that will stimulate re/myelination by promoting neuronal survival, neurite outgrowth, neurogenesis, and/ or oligodendrocyte precursor cell (OPC) survival, proliferation, and/or maturation. Conversely astrocytes that tend to have a more severe "reactive" phenotype, possibly induced by proinflammatory cytokines/CNS tissue damage, may secrete cytokines and chemokines that lead to myelin and oligodendrocyte damage in vitro, suppress remyelination, delay disease recovery in experimental autoimmune encephalomyelitis (EAE), and suppress myelination in myelinating embryonic rat mixed spinal cord cultures. Transplantation of ciliary neurotrophic factor-expressing adult oligodendrocyte precursor cells promotes remyelination and functional recovery after spinal cord injury doi = 10.1016/j.expneurol.2016.03.009 id = cord-023445-c4tqioz1 author = Lauridsen, C. title = Supplementation of Vitamin C to Weaner Diets Increases IgM Concentration and Improves the Biological Activity of Vitamin E in Alveolar Macrophages date = 2008-06-28 keywords = CD8; IFN; IL-12; MBL; TNF; cell summary = We demonstrate that Cw6 þ psoriasis patients had significant CD8 þ T-cell IFN-g responses to peptides from K17 and M6 protein selected on the basis of sequence homology and predicted HLA-Cw*0602 binding. The uptake of MBP by B cells and the presentation of MBP-derive peptides to T helper (Th) cells by B cells may be promoted by the formation of complement (C) activating immune complexes (ICs) between MBP and natural autoantibodies in healthy individuals and disease-associated anti-MBP antibodies in MS patients, respectively. While MBP did not induce measurable proliferation of B cells nor CD4 þ T cells, we observed the production of TNF-a, IFN-g and IL-10 by PBMC in response to incubation with MBP in the presence of sera from healthy controls as well as sera from MS patients. In conclusion, the results of this study suggest an involvement of the ASMase in the activation, expansion or maturation of virus-specific CD8 þ T cells during the acute infection of mice with the LCM virus. doi = 10.1111/j.0300-9475.2004.01423u.x id = cord-009326-dvhkk405 author = Lee, Jae Min title = Broussonetia papyrifera Root Bark Extract Exhibits Anti-inflammatory Effects on Adipose Tissue and Improves Insulin Sensitivity Potentially Via AMPK Activation date = 2020-03-14 keywords = AMPK; PRE; TNF; figure summary = title: Broussonetia papyrifera Root Bark Extract Exhibits Anti-inflammatory Effects on Adipose Tissue and Improves Insulin Sensitivity Potentially Via AMPK Activation PRE inhibited TNF-α-induced NF-κB transcriptional activity in the NF-κB luciferase assay and pro-inflammatory genes'' expression by blocking phosphorylation of IκB and NF-κB in 3T3-L1 adipocytes, which were mediated by activating AMPK. Ten-week-high fat diet (HFD)-fed C57BL6 male mice treated with PRE had improved glucose intolerance and decreased inflammation in adipose tissue, as indicated by reductions in NF-κB phosphorylation and pro-inflammatory genes'' expression. To investigate the effects of PRE on inflammation, we first tested NF-κB transcriptional activity of TPRE because NF-κB is an essential regulator of pro-inflammatory response ( Figure S1 ). Together, these results strongly suggest that PRE suppresses TNF-α-mediated pro-inflammatory gene expression by activating AMPK. Together, these results strongly suggest that PRE suppresses TNF-α-mediated pro-inflammatory gene expression by activating AMPK. doi = 10.3390/nu12030773 id = cord-332071-bqvn3ceq author = Lee, Jeong Seok title = Immunophenotyping of COVID-19 and influenza highlights the role of type I interferons in development of severe COVID-19 date = 2020-07-10 keywords = Fig; IFN; SARS; TNF; covid-19 summary = In a murine model of SARS-CoV infection, a delayed, but considerable type I IFN (IFN-I) response CORONAVIRUS Immunophenotyping of COVID-19 and influenza highlights the role of type I interferons in development of severe COVID-19 (Page numbers not final at time of first release) 2 promotes the accumulation of monocytes-macrophages and the production of pro-inflammatory cytokines, resulting in lethal pneumonia with vascular leakage and impaired virusspecific T-cell responses (10) . To examine the host immune responses in a cell type-specific manner, we subjected 59,572 cells to t-distributed stochastic neighbor embedding (tSNE) based on highly variable genes using the Seurat package (17) and identified 22 different clusters unbiased by patients or experimental batches of scRNA-seq (Fig. 1A, Fig. S1D ). First, we combined both mild and severe COVID-19 as a COVID-19 group and identified disease-specific changes in genes for each cell type compared to the healthy donor group using model-based analysis of single cell transcriptomics (MAST) (18) . doi = 10.1126/sciimmunol.abd1554 id = cord-308008-s2t11l3h author = Limonta, Daniel title = Apoptotic mediators in patients with severe and non‐severe dengue from Brazil date = 2013-10-29 keywords = Survivin; TNF; TRAIL; dengue summary = Therefore, plasma levels of the three proapoptotic mediators Fas ligand (FasL), tumor necrosis factor-a (TNF-a), and TNF-related apoptosis-inducing ligand (TRAIL) were measured in dengue patients. Previous studies of dengue infection have shown apoptosis in lymphocytes [Mongkolsapaya et al., 2003; Myint et al., 2006] , monocytes [Torrentes-Carvalho et al., 2009; Levy et al., 2010] , and peripheral blood mononuclear cells (PBMCs) [Jaiyen et al., 2009] . The other proteins studied, plasma Survivin and PBMCs lysate proteins, are IAPs. Our data suggest that TRAIL could be involved with apoptosis induction of blood lymphocytes and could also contribute to the antiviral response. In the present study, elevated TRAIL levels were observed in patients with dengue without warning signs compared to those with severe dengue and control subjects. The findings in the present work, which used the revised WHO dengue classification, suggest that the antiviral action of TRAIL that was shown previously in cell culture [Warke et al., 2008b] , may also occur in vivo and hence the likely increased severity of dengue in patients lacking an elevated TRAIL production. doi = 10.1002/jmv.23832 id = cord-023935-o2ffxgnn author = Lorts, Angela title = Sepsis date = 2011-12-16 keywords = IL-1; LPS; TNF; response; sepsis; septic; shock summary = SIRS i s a state of infl ammatory/ immune activation and is based on the presence of at least two of the four following clinical criteria: Temperature >38°C or <36°C, heart rate >90th percentile for age, respiratory rate >90th percentile for age, or hyperventilation to PaCO 2 < 32 mm Hg. The defi nition attempts to "capture" all patients at risk for the subsequent development of severe sepsis or septic shock. Among these, the nuclear factor-k B (NF-k b ) and the mitogen activated protein kinase (MAPK) pathways play a prominent role in regulating the expression of a number of infl ammatory gene products key to propagating the sepsis response. Nuclear factork B (NFk b ) and the mitogen activated protein kinase (MAPK) pathways play a prominent role in regulating the expression of a number of infl ammatory gene products key to propagating the sepsis response. doi = 10.1007/978-0-85729-923-9_27 id = cord-002079-jne14jqf author = MacParland, Sonya A. title = Lipopolysaccharide and Tumor Necrosis Factor Alpha Inhibit Interferon Signaling in Hepatocytes by Increasing Ubiquitin-Like Protease 18 (USP18) Expression date = 2016-05-27 keywords = IFN-; LPS; TNF-; usp18 summary = Previous studies from our laboratory have shown that expression of an IFN-stimulated gene (ISG), ubiquitin-like protease (USP)18 is upregulated in chronic HCV infection, leading to impaired hepatocyte responses to IFN-α. We examined the ability of inflammatory stimuli, including tumor necrosis factor alpha (TNF-α), lipopolysaccharide (LPS), interleukin-6 (IL-6) and IL-10 to upregulate hepatocyte USP18 expression and blunt the IFN-α response. Treatment of Huh7.5 cells and primary murine hepatocytes with LPS and TNF-α, but not IL-6 or IL-10, led to upregulated USP18 expression and induced an IFN-α refractory state, which was reversed by USP18 knockdown. These data demonstrate that certain inflammatory stimuli (TNF-␣ and LPS), as well as ischemic injury, but not other cytokines (IL-6 and IL-10) can lead to enhanced hepatocyte USP18 expression and thereby inhibit IFN signaling. Huh7.5 cells and primary murine hepatocytes were treated with IFN-␣ (100 U/ml), TNF-␣ (20 ng/ml), LPS (100 ng/ml), IL-6 (100 ng/ml), or IL-10 (10 ng/ ml) over a 24-h time course, and USP18 expression was determined by quantitative PCR (qPCR) as previously described (8, 9) . doi = 10.1128/jvi.02557-15 id = cord-333650-4towah1t author = Malmo, Jostein title = Cytokine Profiles in Human Metapneumovirus Infected Children: Identification of Genes Involved in the Antiviral Response and Pathogenesis date = 2016-05-12 keywords = IFN; TNF summary = Overall, our data point to cytokines, particularly inflammasome-associated, that might be important in hMPV mediated lung disease and the antiviral response in children with severe infection. To determine the presence of antiviral cytokines in children infected with hMPV and controls, we initially investigated the expression of type I, II and III IFNs. Fig 1A shows that only A2 infected children had slightly elevated mRNA levels of the type I IFN-β compared to the controls. Fig 2 shows the mRNA expression of A) IκBα, a repressor gene induced by NF-κB activation [19] , B) IL-1β, C) IL-18 and D) NLRP3 in hMPV infected children and controls. A previous study comparing the expression of several inflammatory cytokines in hMPV, RSV and influenza virus, detected elevated levels of TNF-α, IL-6 and IL-1β protein in nasal washes from infants with RTI [9] . doi = 10.1371/journal.pone.0155484 id = cord-023373-6wh1kb3p author = Melchjorsen, J. title = Differential Requirements for Toll‐Like Receptor Signalling for Induction of Chemokine Expression by Herpes Simplex Virus and Sendai Virus date = 2008-06-28 keywords = CD8; IFN; IL-12; MBL; TNF; cell summary = We demonstrate that Cw6 þ psoriasis patients had significant CD8 þ T-cell IFN-g responses to peptides from K17 and M6 protein selected on the basis of sequence homology and predicted HLA-Cw*0602 binding. The uptake of MBP by B cells and the presentation of MBP-derive peptides to T helper (Th) cells by B cells may be promoted by the formation of complement (C) activating immune complexes (ICs) between MBP and natural autoantibodies in healthy individuals and disease-associated anti-MBP antibodies in MS patients, respectively. While MBP did not induce measurable proliferation of B cells nor CD4 þ T cells, we observed the production of TNF-a, IFN-g and IL-10 by PBMC in response to incubation with MBP in the presence of sera from healthy controls as well as sera from MS patients. In conclusion, the results of this study suggest an involvement of the ASMase in the activation, expansion or maturation of virus-specific CD8 þ T cells during the acute infection of mice with the LCM virus. doi = 10.1111/j.0300-9475.2004.01423r.x id = cord-354492-6r6qs4pp author = Messina, Giovanni title = Functional Role of Dietary Intervention to Improve the Outcome of COVID-19: A Hypothesis of Work date = 2020-04-28 keywords = COVID-19; IL-6; TNF; adiponectin; infection; role summary = Considering that the COVID-19 infection can generate a mild or highly acute respiratory syndrome with a consequent release of pro-inflammatory cytokines, including IL-6 and TNF-α, a dietary regimen modification in order to improve the levels of adiponectin could be very useful both to prevent the infection and to take care of patients, improving their outcomes. In human infections with highly virulent respiratory viruses-such as avian influenza H5N1, H7N9, Severe Acute Respiratory Syndrome (SARS) coronavirus, and Coronavirus Disease-19 (COVID-19)-immunopathogenesis caused by the overproduction of pro-inflammatory cytokines may play an essential role in disease progression and mortality [3] . Finally, considering that the COVID-19 infection can generate a mild or highly acute respiratory syndrome with a consequent release of pro-inflammatory cytokines, including IL-6 and TNF-α, a modification of the dietary regimen in order to improve the levels of adiponectin could be very useful both to prevent the infection and to take care of the patients, improving their outcomes. doi = 10.3390/ijms21093104 id = cord-319121-et957lfl author = Mifflin, Lauren title = Receptor-interacting protein kinase 1 (RIPK1) as a therapeutic target date = 2020-07-15 keywords = A20; NEMO; RIPK1; TNF; TNFAIP3; activation; disease summary = However, as researchers continued to delve into the mechanisms governed by RIPK1, it has become apparent that RIPK1 inhibitors may offer key therapeutic options that anti-TNF therapies do not: first, RIPK1 inhibitors are safe in the central nervous system (CNS) as RIPK1 kinase does not signal through TNFR2 which has a protective role in the CNS 7 ; second, RIPK1 participates in a broader set of pro-inflammatory activities than those restricted to TNF 8 ; third, RIPK1 is regulated by a distinct set of signalling molecules that are genetically implicated in human autoimmune and autoinflammatory diseases, as discussed below, and thus patient stratification may be important in conducting clinical trials of RIPK1 inhibitors. Mouse models with cell lineage-specific A20 deficiency phenocopy different human inflammatory diseases, suggesting an important role for A20 in restricting RIPK1 activation in multiple tissues ( showed increased levels of pro-inflammatory cytokines, such as TNF, IL-1β and IL-6, and demonstrated clinical improvement after treatment with anti-TNF or anti-IL-1β therapy. doi = 10.1038/s41573-020-0071-y id = cord-276564-o21ncldx author = Miller, R. title = COVID-19: NAD(+) deficiency may predispose the aged, obese and type2 diabetics to mortality through its effect on SIRT1 activity date = 2020-06-29 keywords = NAD; TNF; sirt1 summary = This hypothesis suggests that a deficiency of nicotinamide adenine dinucleotide (NAD + ) may be the primary factor related to the SARS-Cov-2 disease spectrum and the risk for mortality, as subclinical nutritional deficiencies may be unmasked by any significant increase in oxidative stress. This hypothesis suggests that a deficiency of nicotinamide adenine dinucleotide (NAD + ) may be the primary factor related to the SARS-Cov-2 disease spectrum and the risk for mortality, as subclinical nutritional deficiencies may be unmasked by any significant increase in oxidative stress. Vulnerable patient groups would potentially be less likely or unable to ensure sufficient activation of SIRT1 due to low NAD + levels or associated nutritional deficiencies including Zn ++ , and as such contribute to an inability to control viral replication and reduce the uncontrolled expression of pro-inflammatory cytokines. doi = 10.1016/j.mehy.2020.110044 id = cord-020643-0yzkqykg author = Müller-Werdan, U. title = Schock date = 2006 keywords = Abschn; Einsatz; Gabe; Herz; Letalität; Lösungen; MODS; PCI; Patienten; Schock; Score; TNF; Therapie; Werdan; als; auf; bei; den; der; des; die; durch; eine; ist; kann; mit; nicht; sepsis; und; von; zur summary = Auch dass nichtinfektiöse Noxen (Trauma, Pankreatitis, herzchirurgische Operationen mit der Herz-Lungen-Maschine) zu einem ganz ähnlichen klinischen Bild wie bei bakteri-ell ausgelöster Sepsis und septischem Schock führen können, spricht für eine mehr oder weniger gemeinsame Zytokin-/Mediatorendstrecke als verantwortliche Schädigungskaskade sowohl bei infektiösen als auch bei nichtinfektiösen (SIRS, . Eine Ausnahme von dieser Regel stellt die Hirndurchblutung dar, die in der Sepsis weiterhin die Fähigkeit zur Autoregulation beibehält: Bei Patienten mit Sepsis ist die Hirndurchblutung bereits vor der Ausbildung des Schockzustandes um ein Drittel reduziert, wobei diese Durchblutungseinschränkung jedoch nicht als Ursache der septischen Enzephalopathie angesehen wird. Im Koronargefäßsystem fällt dagegen der Widerstand noch stärker ab als in den anderen Organen und demzufolge ist die Koronarperfusion bei Patienten mit septischem Schock sogar häufi g erhöht (Dhainaut et al. Die Messung des zentralen Venendrucks ist bei kritisch Kranken, insbesondere Schockpatienten, für das hämodynamische Monitoring normalerweise nicht genügend, eine Abschätzung der linksventrikulären Vorlast kann damit nicht ausreichend sicher durchgeführt werden, ebenso wenig wie mit der klinischen Einschätzung allein. doi = 10.1007/3-540-29425-2_6 id = cord-340741-bhxm4zua author = Nayak, Tapas Kumar title = P38 and JNK Mitogen-Activated Protein Kinases Interact With Chikungunya Virus Non-structural Protein-2 and Regulate TNF Induction During Viral Infection in Macrophages date = 2019-04-12 keywords = CHIKV; Chikungunya; JNK; TNF summary = title: P38 and JNK Mitogen-Activated Protein Kinases Interact With Chikungunya Virus Non-structural Protein-2 and Regulate TNF Induction During Viral Infection in Macrophages Additionally, it was noticed that the expressions of key transcription factors involved mainly in antiviral responses (p-IRF3) and TNF production (p-c-jun) were induced significantly in the CHIKV infected macrophages as compared to the corresponding mock cells. In summary, for the first time it has been shown that CHIKV triggers robust TNF production in the host macrophages via both p-p38 and p-JNK/p-c-jun pathways and the interaction of viral protein, nsP2 with these MAPKs during infection. In summary, for the first time it has been shown that CHIKV triggers robust TNF production (a key mediator of CHIKV induced inflammation) in the host macrophages via both p-p38 and p-JNK/p-c-jun pathways and viral protein nsP2 interacts with both the MAPKs during infection. doi = 10.3389/fimmu.2019.00786 id = cord-023430-5zuewjv2 author = Nilkaeo, A. title = Interleukin‐18 Inhibition of Oral Carcinoma Cell Proliferation date = 2008-06-28 keywords = CD8; IFN; IL-12; MBL; TNF; cell summary = We demonstrate that Cw6 þ psoriasis patients had significant CD8 þ T-cell IFN-g responses to peptides from K17 and M6 protein selected on the basis of sequence homology and predicted HLA-Cw*0602 binding. The uptake of MBP by B cells and the presentation of MBP-derive peptides to T helper (Th) cells by B cells may be promoted by the formation of complement (C) activating immune complexes (ICs) between MBP and natural autoantibodies in healthy individuals and disease-associated anti-MBP antibodies in MS patients, respectively. While MBP did not induce measurable proliferation of B cells nor CD4 þ T cells, we observed the production of TNF-a, IFN-g and IL-10 by PBMC in response to incubation with MBP in the presence of sera from healthy controls as well as sera from MS patients. In conclusion, the results of this study suggest an involvement of the ASMase in the activation, expansion or maturation of virus-specific CD8 þ T cells during the acute infection of mice with the LCM virus. doi = 10.1111/j.0300-9475.2004.01423bg.x id = cord-006610-me8rhkcg author = Nör, Jacques E. title = Role of endothelial cell survival and death signals in angiogenesis date = 1999 keywords = Bcl-2; TNF; VEGF; apoptosis; cell; endothelial summary = There is now convincing evidence that regulated patterns of endothelial cell survival and death, a process known as apoptosis, play a central role in the periodic remodeling of the vasculature, and in the timely evolution and regression of angiogenic responses. In this review we discuss the current evidence suggesting a role for inducers and inhibitors of angiogenesis as well as other mediators that modify endothelial cells functions in the survival and death of endothelial cells. Events that govern the survival and death of endothelial cells have emerged as major factors that contribute to angiogenic responses during embryonic development, in the maintenance of organ and tissue homeostasis in adult organisms, and in pathological conditions such as tumor development. Enhanced activity of protein kinase C was associated with the ability of bFGF to protect endothelial cells against apoptosis induced by growth factor deprivation [170] or ionizing radiation in vitro and in vivo [170±172]. Vascular Endothelial Growth Factor (VEGF)-mediated angiogenesis is associated with enhanced endothelial cell survival and induction of Bcl-2 expression doi = 10.1023/a:1009053411094 id = cord-280599-7ixpqd5n author = OPENSHAW, P J M title = What does the peripheral blood tell you in SARS? date = 2004-04-01 keywords = TNF summary = However, cytokine release is often very local, as illustrated by studies of TNF production in patients with bacterial pneumonia that show TNF levels to be high in bronchial lavage fluid from the affected lung, but not in fluid from the contralateral lung or in serum [4] . More importantly, anti-TNF therapy works well in many patients with rheumatoid arthritis or juvenile RA, but measurement of cytokines in serum and synovial fluid does not show raised levels of TNF [9] . So, what can we expect to learn by profiling cytokine production or levels in blood samples from patients with inflammatory diseases? Prolonged disturbances of in vitro cytokine production in patients with severe acute respiratory syndrome (SARS) treated with ribavirin and steroids Comparison of systemic cytokine levels in patients with acute respiratory distress syndrome, severe pneumonia, and controls doi = 10.1111/j.1365-2249.2004.02448.x id = cord-283246-dj7teo89 author = Otsuka, Ryo title = Macrophage activation syndrome and COVID-19 date = 2020-08-06 keywords = COVID-19; MAS; TNF summary = Still, it is possible that the causative virus for COVID-19, SARS-CoV-2, infect with particular types of cells such as endothelial vessels in the lung, or alveolar wall or macrophages. MAS is typified by markedly upregulated expression of pro-inflammatory cytokines, which is called "cytokine storm." Without any therapeutic intervention, this strong inflammation results in severe tissue injury and, ultimately, patient death. Thus, the commencement of local inflammation induced by SARS-CoV-2 infection activates macrophages at that site, spreading rapidly to the entire lung, possibly due to the abundant expression of virus entry receptors, ACE2 and TMPRSS2 [36] . Severe cases of COVID-19 are often observed with ARDS, representing the MAS-like clinical and laboratory features. The role of cytokines including interleukin-6 in COVID-19 induced pneumonia and macrophage activation syndrome-like disease Tocilizumab for the treatment of severe COVID-19 pneumonia with hyperinflammatory syndrome and acute respiratory failure: a single center study of 100 patients in doi = 10.1186/s41232-020-00131-w id = cord-297857-ybqj8z1r author = Petagna, L. title = Pathophysiology of Crohn’s disease inflammation and recurrence date = 2020-11-07 keywords = Crohn; TNF; disease; recurrence summary = Crohn''s disease evolution is mediated by a complex alteration of the inflammatory response which is characterized by alterations of the innate immunity of the intestinal mucosa barrier together with a remodeling of the extracellular matrix through the expression of metalloproteins and increased adhesion molecules expression, such as MAcCAM-1. The pathogenesis is also sustained by the interaction of these cells with integrins, adhesion molecules and multiple chemokines, responsible for the production of elevated levels of inflammatory cytokines, representing the target of immune and non-immune cells and the promotion of mucosal inflammation. A new Antimesenteric functional end-to-end Handsewn anastomosis: surgical prevention of anastomotic recurrence in Crohn''s disease Surgical recurrence at anastomotic site after bowel resection in Crohn''s disease: comparison of Kono-S and end-to-end anastomosis Surgical prevention of anastomotic recurrence by excluding mesentery in Crohn''s disease: the SuPREMe-CD study -a randomized clinical trial Inclusion of the mesentery in Ileocolic resection for Crohn''s disease is associated with reduced surgical recurrence doi = 10.1186/s13062-020-00280-5 id = cord-295523-5pv7kw6i author = Picchianti Diamanti, Andrea title = Cytokine Release Syndrome in COVID-19 Patients, A New Scenario for an Old Concern: The Fragile Balance between Infections and Autoimmunity date = 2020-05-08 keywords = COVID-19; CRS; IL-6; SARS; TNF; patient summary = However, in about 20% of patients, the infection progresses to severe interstitial pneumonia and can induce an uncontrolled host-immune response, leading to a life-threatening condition called cytokine release syndrome (CRS). We critically review the rationale for the adoption of immunosuppressive agents, commonly used in autoimmune diseases, in the treatment of SARS-CoV-2 infection and report current knowledge of ongoing studies. The exacerbated reaction to infections or to biological therapy is caused by the rapid recruitment of macrophages and neutrophils, which produce pro-inflammatory cytokines and alter the fragile balance between a controlled immune response and a host-damaging reaction. As of now, four clinical trials are recruiting patients with COVID-19, severe acute respiratory failure, and CRS, aiming at evaluating the safety and effectiveness of anakinra alone or in combination with anti-IL-6 agents (NCT04330638, NCT0432402, NCT04357366, NCT04339712). High disease activity is associated with an increased risk of infection in patients with rheumatoid arthritis doi = 10.3390/ijms21093330 id = cord-005664-n4xv247l author = Plötz, Frans B. title = Mechanical ventilation alters the immune response in children without lung pathology date = 2002-01-15 keywords = IFN; TNF; th1 summary = In the tracheal aspirates the immune balance was characterized by a proinflammatory response pattern, with a significant increase in TNF-α and IL-6 concentrations; concentrations of anti-inflammatory mediators remained very low. Conclusions: Two hours of servoflurane and mechanical ventilation using a tidal volume of 10 ml/kg is associated with remarkable changes in the immune response in infants without preexisting lung pathology undergoing cardiac catheterization. Conclusions: Two hours of servoflurane and mechanical ventilation using a tidal volume of 10 ml/kg is associated with remarkable changes in the immune response in infants without preexisting lung pathology undergoing cardiac catheterization. The major finding of the present study is that exposing infants with normal lung function to 2 h of volatile anesthetics, mechanical ventilation, and cardiac catheterization is associated with remarkable changes in immune responses. We observed a proinflammatory response in the lungs with a significant increase in TNF-α, while antiinflammatory cytokine concentrations in tracheal aspirates remained virtually unchanged, just above the detection level. doi = 10.1007/s00134-002-1216-7 id = cord-324949-sqy03dks author = Poe, Francis L. title = N-Acetylcysteine: a potential therapeutic agent for SARS-CoV-2 date = 2020-05-30 keywords = NAC; SARS; TNF summary = In vivo, in vitro, and human clinical trials have demonstrated N-acetylcysteine (NAC) as an effective method of improving redox status, especially when under oxidative stress. Mediation of the viral load could occur through NAC''s ability to increase cellular redox status via maximizing the rate limiting step of glutathione synthesis, and thereby potentially decreasing the effects of virally induced oxidative stress and cell death. The pathogenic factors of SARS-CoV-2 that could possibly be mediated by NAC are (1) T cell exhaustion, which manifests as lower counts and decreased functional capacity of CD4+ and CD8+ cells; (2) pro-inflammatory state via increase in TNF-ɑ, IL1β, IL18; and (3) modulation of viral activity through increased glutathione. Mediation of the viral load could occur through the ability of NAC to increase cellular redox status by maximizing the rate limiting step of glutathione synthesis, and thereby decreasing the effects of virally induced oxidative stress and cell death. doi = 10.1016/j.mehy.2020.109862 id = cord-271812-ldwb05xn author = Prasad, Ananda S. title = Discovery of Human Zinc Deficiency: Its Impact on Human Health and Disease(1)(2)(3) date = 2013-03-01 keywords = TNF; Wilson; cell; decrease; deficiency; zinc summary = Zinc has been very successfully used as a therapeutic modality for the management of acute diarrhea in children, Wilson''s disease, the common cold and for the prevention of blindness in patients with age-related dry type of macular degeneration and is very effective in decreasing the incidence of infection in the elderly. AE is a lethal, autosomal, recessive trait that usually occurs in infants of Italian, Armenian, or Iranian lineage 4 Abbreviations used: AB, b amyloid protein; AD, Alzheimer''s disease; AE, acrodermatitis enteropathica; APP, amyloid precursor protein; CRP, C-reactive protein; DC, dendritic cells; HAE, 4-hydroxyalkenal; HAEC, human vascular endothelial cell; HL-60, human promyelocytic leukemia cell line; ICAM-1, intercellular adhesion molecule 1; IFN, interferon; IGF-1, insulin-like growth factor 1; MDA, malondialdehyde; MNC, mononuclear cell; NF-kB, nuclear factor kB; oxLDL, oxidized LDL; PHA-P, phytohemagglutinin P; PMA, phorbol-12 myristate 13 acetate; ra, receptor antagonist; RDA, recommended daily allowance; ROS, reactive oxygen species; SCD, sickle cell disease; sIL-1 ra, soluble interleukin-1 receptor antagonist; THP-1, human monocytic leukemia cell line; TK, deoxythymidine kinase; VCAM-1, vascular cell adhesion molecule 1. doi = 10.3945/an.112.003210 id = cord-301102-jbjysyqm author = Priestnall, Simon L. title = Quantification of mRNA encoding cytokines and chemokines and assessment of ciliary function in canine tracheal epithelium during infection with canine respiratory coronavirus (CRCoV) date = 2009-01-15 keywords = IL-6; PCR; TNF; culture summary = title: Quantification of mRNA encoding cytokines and chemokines and assessment of ciliary function in canine tracheal epithelium during infection with canine respiratory coronavirus (CRCoV) This study aimed to quantify pro-inflammatory cytokine mRNAs following infection of canine air-interface tracheal cultures with CRCoV. This study aimed to quantify pro-inflammatory cytokine mRNAs following infection of canine air-interface tracheal cultures with CRCoV. The quantification of canine IL-6, IL-8 and TNF-a mRNA copies in CRCoV-inoculated cultures was presented as the logarithm of the fold change relative to control-inoculated cultures in the same dog at the same time point. In response to LPS, mRNA levels of TNF-a, IL-6 and IL-8 in cultures, were significantly increased from 24 h post-inoculation, relative to controls, indicating that the assay was sensitive enough to detect changes in cytokine mRNAs within this system. IHC revealed coronavirus antigen positive intra-cytoplasmic staining of ciliated epithelial and goblet cells within canine tracheas of both CRCoV-inoculated cultures and from naturally infected cases of CIRD. doi = 10.1016/j.vetimm.2008.09.017 id = cord-023372-ft8cp9op author = Rahman, Q. K. title = The Immunomodulatory Effect of Heat Shock Protein 70: Immunization with a DNA Construct Based on the Malarial Antigen Fused with a Fragment of HSP 70 Primes for a Th‐1 Type of Response date = 2008-06-28 keywords = CD8; IFN; IL-12; MBL; TNF; cell summary = We demonstrate that Cw6 þ psoriasis patients had significant CD8 þ T-cell IFN-g responses to peptides from K17 and M6 protein selected on the basis of sequence homology and predicted HLA-Cw*0602 binding. The uptake of MBP by B cells and the presentation of MBP-derive peptides to T helper (Th) cells by B cells may be promoted by the formation of complement (C) activating immune complexes (ICs) between MBP and natural autoantibodies in healthy individuals and disease-associated anti-MBP antibodies in MS patients, respectively. While MBP did not induce measurable proliferation of B cells nor CD4 þ T cells, we observed the production of TNF-a, IFN-g and IL-10 by PBMC in response to incubation with MBP in the presence of sera from healthy controls as well as sera from MS patients. In conclusion, the results of this study suggest an involvement of the ASMase in the activation, expansion or maturation of virus-specific CD8 þ T cells during the acute infection of mice with the LCM virus. doi = 10.1111/j.0300-9475.2004.01423aw.x id = cord-103625-p55ew8w7 author = Ramana, Chilakamarti V. title = Regulation of early growth response-1 (Egr-1) gene expression by Stat1-independent type I interferon signaling and respiratory viruses date = 2020-08-14 keywords = Egr-1; IFN; TNF summary = Transcriptional factor profiling in the transcriptome and RNA analysis revealed that Early growth response-1 (Egr-1) was rapidly induced by IFN-α/β and Toll-like receptor (TLR) ligands in multiple cell types. Furthermore, Egr-1 inducible genes including transcription factors, mediators of cell growth, and chemokines were differentially regulated in the human lung cell lines after coronavirus infection, and in the lung biopsies of COVID-19 patients. In this study, transcription factor profiling in interferon-mediated gene expression data sets and RT-PCR revealed that Egr-1 was rapidly induced by IFN-α/β and TLR ligands in multiple cell types. Respiratory pathogens including coronaviruses (SARS-CoV-1 and 2) and influenza viruses regulated the expression of Egr-1 in human lung cell lines and in lung biopsies and peripheral blood cells of COVID-19 patients, These studies suggest that the regulation of Egr-1 may play an important role in the antiviral response and inflammatory disease. doi = 10.1101/2020.08.14.244897 id = cord-013366-sbdtpsz6 author = Ramírez-Pérez, Sergio title = Downregulation of Inflammatory Cytokine Release from IL-1β and LPS-Stimulated PBMC Orchestrated by ST2825, a MyD88 Dimerisation Inhibitor date = 2020-09-21 keywords = LPS; PBMC; ST2825; TNF summary = Myeloid differentiation primary response 88 (MyD88) is an essential protein recruited after lipopolysaccharide (LPS) and interleukin (IL)-1β stimulation, a process that converges in nuclear factor kappa B (NF-κB) activation, as well as a transcription of several genes of both proand anti-inflammatory cytokines. The chemical molecule ST2825 acts as an inhibitor of MyD88 dimerisation and its activity has been demonstrated through the inhibition of TLR9-dependent CpG-regulated signalling, and inhibition of IL-12, IL-1β, IL-6 and tumor necrosis factor alpha (TNF-α) expression in LPS-stimulated RAW 264.7 cells [19] [20] [21] [22] . The present study shows that the specific inhibition of critical components in the IL-1 signalling pathway is not enough to avoid the secretion of inflammatory mediators, the above suggests that various MyD88-independent mechanisms could regulate the production of cytokines in PBMC. doi = 10.3390/molecules25184322 id = cord-269986-jdcw59r2 author = Regan, Andrew D. title = Activation of p38 MAPK by feline infectious peritonitis virus regulates pro-inflammatory cytokine production in primary blood-derived feline mononuclear cells date = 2009-02-05 keywords = FIPV; MAPK; PFBM; tnf summary = Here we show that infection of primary blood-derived feline mononuclear cells by FIPV WSU 79-1146 and FIPV-DF2 leads to rapid activation of the p38 MAPK pathway and that this activation regulates production of the pro-inflammatory cytokine tumor necrosis factor alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta). FIPV-induced p38 MAPK activation was observed in primary feline blood-derived mononuclear cells individually purified from multiple SPF cats, as was the inhibition of TNF-alpha production by pyridinyl imidazole inhibitors. To determine whether viral replication was required for FIPV-induced p38 MAPK activation, UV-inactivated virus was added to PFBM cells and analyzed by western blot as described above (Fig. 1B) . Overall these data indicate that production of the pro-inflammatory cytokine TNF-alpha in FIPVinfected PFBM cells is regulated by activation of the p38 MAPK pathway. In this study we show that infection by FIPV causes a rapid activation the p38 MAPK pathway in PFBM cells, and that this process directly regulates production of the pro-inflammatory cytokines TNF-alpha and IL-1 beta. doi = 10.1016/j.virol.2008.11.006 id = cord-023402-8qfmo6rq author = Reinholdt, J. title = Pneumococcal IgA1 Protease Activity Interferes with Opsonophagocytosis of Streptococcus Pneumoniae Mediated by Serotype‐Specific Human Monoclonal IgA1 Antibodies date = 2008-06-28 keywords = CD8; IFN; IL-12; MBL; TNF; cell summary = We demonstrate that Cw6 þ psoriasis patients had significant CD8 þ T-cell IFN-g responses to peptides from K17 and M6 protein selected on the basis of sequence homology and predicted HLA-Cw*0602 binding. The uptake of MBP by B cells and the presentation of MBP-derive peptides to T helper (Th) cells by B cells may be promoted by the formation of complement (C) activating immune complexes (ICs) between MBP and natural autoantibodies in healthy individuals and disease-associated anti-MBP antibodies in MS patients, respectively. While MBP did not induce measurable proliferation of B cells nor CD4 þ T cells, we observed the production of TNF-a, IFN-g and IL-10 by PBMC in response to incubation with MBP in the presence of sera from healthy controls as well as sera from MS patients. In conclusion, the results of this study suggest an involvement of the ASMase in the activation, expansion or maturation of virus-specific CD8 þ T cells during the acute infection of mice with the LCM virus. doi = 10.1111/j.0300-9475.2004.01423t.x id = cord-007613-g4s0v8ra author = Rimstad, Espen title = Cloning, expression and characterization of biologically active feline tumour necrosis factor-α date = 2000-03-10 keywords = Fig; GST; TNF; dna summary = To assure that stimulated macrophage mRNA was the actual source for cDNA, cDNA derived by reverse transcription of mRNA from unstimulated macrophage cultures, as well as feline genomic DNA, were extracted and used as targets in separate and parallel PCRs. The amplified fragments generated by both the P 1 /P3 and P2/P3 primers were separately cloned into the plasmid vector pCRI1 (TA-cloning kit, Invitrogen), and the nucleotide sequences were determined by conventional dideoxy sequencing of both strands. Although some variation was evident between the four individual donor cats, rfTNF-a induced a dose related increase of IG2R and MHC class II antigen expression on the cell surface of in vitro stimulated feline PMBCs (Fig. 6 ) . Tumor necrosis factor a induces expression of human immunodeticiency virus in a chronically infected T-cell clone Tumor necrosis factor a induces proteins that bind specifically to kB-like enhancer elements and regulate interleukin 2 receptor a-chain gene expression in primary human T-lymphocytes doi = 10.1016/0165-2427(94)05345-s id = cord-308433-vrkdtrfz author = Roberts, Ceri A. title = TNF Blockade Maintains an IL-10(+) Phenotype in Human Effector CD4(+) and CD8(+) T Cells date = 2017-02-15 keywords = CD4; IL-10; TNF summary = Addition of the TNFi drug adalimumab to anti-CD3-stimulated human CD4 + T cell/monocyte cocultures led to increased percentages of IL-10 + cells in pro-inflammatory IL-17 + , IFNγ + , TNFα + , GM-CSF + , and IL-4 + CD4 + T cell subpopulations. Addition of the TNFi drug adalimumab to anti-CD3-stimulated human CD4 + T cell/monocyte cocultures led to increased percentages of IL-10 + cells in pro-inflammatory IL-17 + , IFNγ + , TNFα + , GM-CSF + , and IL-4 + CD4 + T cell subpopulations. To investigate whether TNF blockade regulates IL-10 expression in different pro-inflammatory cytokine-producing CD4 + T cells, we isolated CD4 + T cells from PB of healthy donors and cocultured the cells with CD14 + monocytes and anti-CD3 mAb (100 ng/ml) in the absence or presence of the anti-TNF mAb adalimumab (1 µg/ml), as previously described (20) . doi = 10.3389/fimmu.2017.00157 id = cord-006770-m5wqk6rh author = Rook, Graham A. W. title = Evaluation of TNF as antiviral, antibacterial and antiparasitic agent date = 1991 keywords = TNF; factor; necrosis; tumour summary = On the other hand such antibody had little effect if given on day 3 or later, suggesting that the protective role of TNF is mostly during the early phase of the infection. Effect of recombinant tumour necrosis factor on acute infection in mice with toxoplasma gondii or Trypanosoma cruzi Protective effects of tumor necrosis factor in experimental LegioneUa pneumophila infections of mice via activation of PMN function Production of tumor necrosis factor alpha and interteukin 1 beta by monocytic cells infected with human immunodeficiency virus The in vitro antiviral activity of tumor necrosis factor (TNF) in WISH cells is mediated by IFN-beta induction Human tumour necrosis factor alpha kills herpesvirus-infected, but not normal cells Cytocidal effect of tumor necrosis factor on cells chronically infected with human immunodeficiency virus (HIV): enhancement of HIV replication Tumor necrosis factor alpha induces expression of human immunodeficiency virus in a chronically infected T-cell clone doi = 10.1007/bf02172089 id = cord-275413-e2rhioty author = Rowland, Raymond R.R. title = The interaction between PRRSV and the late gestation pig fetus date = 2010-09-09 keywords = IFN-; PCR; PRRSV; TNF-; fetus summary = The purpose of this study was to characterize the interaction between PRRSV and the pig fetus by (1) identifying sites of virus replication, (2) measuring immune and inflammatory cytokines in different compartments, and (3) evaluating the response of lymph nodes. Maternal, accessory and fetal tissues were collected and stored in formalin for histological staining and immunohistochemistry (IHC), or storage in RNAlater (Ambion) for RT-PCR of cytokine mRNAs. PRRSV-specific antibody was measured in sera using the HerdCheck ® PRRS ELISA (IDEXX) and performed by personnel at Kansas State University Veterinary Diagnostic Laboratory. As shown in Fig. 4A , IFN-␥ and TNF-␣ PCR products were not detected in lung, lymph node or placenta from the non-infected fetuses. To determine if cytokine gene expression was the direct result of PRRSV infection, RT-PCR for IFN-␥ and TNF-␣ was performed on the same tissues from fetuses of infected dam no. doi = 10.1016/j.virusres.2010.09.001 id = cord-023429-x52gbklw author = Ruseva, M. title = Mannan‐Binding Lectin Inhibits Humoural Responses date = 2008-06-28 keywords = CD8; IFN; IL-12; MBL; TNF; cell summary = We demonstrate that Cw6 þ psoriasis patients had significant CD8 þ T-cell IFN-g responses to peptides from K17 and M6 protein selected on the basis of sequence homology and predicted HLA-Cw*0602 binding. The uptake of MBP by B cells and the presentation of MBP-derive peptides to T helper (Th) cells by B cells may be promoted by the formation of complement (C) activating immune complexes (ICs) between MBP and natural autoantibodies in healthy individuals and disease-associated anti-MBP antibodies in MS patients, respectively. While MBP did not induce measurable proliferation of B cells nor CD4 þ T cells, we observed the production of TNF-a, IFN-g and IL-10 by PBMC in response to incubation with MBP in the presence of sera from healthy controls as well as sera from MS patients. In conclusion, the results of this study suggest an involvement of the ASMase in the activation, expansion or maturation of virus-specific CD8 þ T cells during the acute infection of mice with the LCM virus. doi = 10.1111/j.0300-9475.2004.01423an.x id = cord-023425-3sjsogvq author = Røntved, C. M. title = Do High and Low Tumour Necrosis Factor‐α Responders Exist in Dairy Cows? date = 2008-06-28 keywords = CD8; IFN; IL-12; MBL; TNF; cell summary = doi = 10.1111/j.0300-9475.2004.01423v.x id = cord-020757-q4ivezyq author = Saikumar, Pothana title = Apoptosis and Cell Death: Relevance to Lung date = 2010-05-21 keywords = Fas; TNF; apoptosis; cell; death; protein summary = The extrinsic pathway involves binding of death ligands such as tumor necrosis factor-α (TNF-α), CD95 ligand (Fas ligand), and TNF-related apoptosis-inducing ligand (TRAIL) to their cognate cell surface receptors TNFR1, CD95/Fas, TRAIL-R1, TRAIL-R2, and the DR series of receptors, 29 resulting in the activation of initiator caspase-8 (also known as FADD-homologous ICE/CED-3-like protease or FLICE) and subsequent activation of effector caspase-3 ( Figure 4 .2). In cytotoxic T lymphocyte-induced death, granzyme B, which enters the cell through membrane channels formed by the protein perforin, activates caspases by cleaving them directly or indirectly. Intracellular Pathways: Lack of survival stimuli (withdrawal of growth factor, hypoxia, genotoxic substances, etc.) is thought to generate apoptotic signals through ill-defi ned mechanisms, which lead to translocation of proapoptotic proteins such as Bax to the outer mitochondrial membrane. For example, agents that damage DNA, such as ionizing radiation and certain xenobiotics, lead to activation of p53-mediated mechanisms that commit cells to apoptosis, at least in part through transcriptional upregulation of proapoptotic proteins. doi = 10.1007/978-0-387-72430-0_4 id = cord-313227-6zwkfzab author = Scala, Stefania title = Fighting the Host Reaction to SARS-COv-2 in Critically Ill Patients: The Possible Contribution of Off-Label Drugs date = 2020-05-27 keywords = IL-6; SARS; TNF; patient summary = Interestingly, in patients infected by SARS-COv-2, there is an increase in IL1β, IFNγ, IP10, and MCP1, probably leading to activated T-helper-1 (TH1) cell responses, and increased production of T-helper-2 (TH2) immunosuppressive cytokines, such as IL4 and IL10 (18) . Peripheral blood examinations on admission in the majority of patients with COVID-19 displayed lymphopenia, elevated infection-related biomarkers (i.e., procalcitonin, erythrocyte sedimentation rate, serum ferritin, and C-reactive protein) (20) and several elevated inflammatory cytokines (i.e., tumor necrosis factor (TNF)-α, interleukin (IL)-2R and IL-6). Despite markedly reducing virus titers, anti-S-IgG caused lung injury during the early stages of infection, impairing the wound-healing macrophage response and TGF-β production, while promoting pro inflammatory cytokine IL-8, MCP1 production, and inflammatory macrophage accumulation (22) . Another proteasome inhibitor, VR23, possess powerful antiinflammatory activity reducing IL-6 in synovial cells from RA patients, and improving LPS-induced acute lung injury by decreasing neutrophil migration, TNF-α secretion, and tissue inflammation in a mice model (52) . doi = 10.3389/fimmu.2020.01201 id = cord-023950-nv0pbbu2 author = Schnyder, Bruno title = Dual Role of Th17 Cytokines, IL-17A,F, and IL-22 in Allergic Asthma date = 2012-07-19 keywords = IL-17A; IL-22; TNF summary = Unchecked activation of Th17 cells by IL-23 is linked to chronic inflammation in experimental autoimmune encephalomyelitis (EAE) and type II collagen-induced arthritis, two heretofore prototypical "Th1" disease models [6, 7] . Furthermore, Murdoch and Lloyd provide evidence in the model of acute allergen-induced response that the gdT cell-dependent normalization of lung function and resolution of inflammation was dependent on the production of IL-17 [16] . These data provide evidence that IL-17A,F and IL-22 besides their inflammatory role have a negative regulatory function in allergic lung inflammation. On a mechanistic level, IL-17A elicits dual effects and reportedly promotes expression of proinflammatory (hemopoietic, CXC-chemokines, acute phase) factors [54, 55] , whereas it inhibits the production of mononuclear cell recruiting molecules like TNF-induced VCAM-1 and CC-chemokine RANTES [35] . IL-22 attenuates IL-25 production by lung epithelial cells and inhibits antigen-induced eosinophilic airway inflammation doi = 10.1007/978-3-0348-0522-3_10 id = cord-023433-d1b7qvhs author = Siassi, M. title = Expression of Human Collectins in Colorectal Carcinoma date = 2008-06-28 keywords = CD8; IFN; IL-12; MBL; TNF; cell summary = We demonstrate that Cw6 þ psoriasis patients had significant CD8 þ T-cell IFN-g responses to peptides from K17 and M6 protein selected on the basis of sequence homology and predicted HLA-Cw*0602 binding. The uptake of MBP by B cells and the presentation of MBP-derive peptides to T helper (Th) cells by B cells may be promoted by the formation of complement (C) activating immune complexes (ICs) between MBP and natural autoantibodies in healthy individuals and disease-associated anti-MBP antibodies in MS patients, respectively. While MBP did not induce measurable proliferation of B cells nor CD4 þ T cells, we observed the production of TNF-a, IFN-g and IL-10 by PBMC in response to incubation with MBP in the presence of sera from healthy controls as well as sera from MS patients. In conclusion, the results of this study suggest an involvement of the ASMase in the activation, expansion or maturation of virus-specific CD8 þ T cells during the acute infection of mice with the LCM virus. doi = 10.1111/j.0300-9475.2004.01423bo.x id = cord-023431-zjyrhlxn author = Sigmundsdóttir, H. title = Differential Effects of Interleukin‐12 and Interleukin‐10 on Superantigen‐Induced Expression of Cutaneous Lymphocyte‐Associated Antigen and αEβ7 Integrin (CD103) by CD8(+) T cells date = 2008-06-28 keywords = CD8; IFN; IL-12; MBL; TNF; cell summary = We demonstrate that Cw6 þ psoriasis patients had significant CD8 þ T-cell IFN-g responses to peptides from K17 and M6 protein selected on the basis of sequence homology and predicted HLA-Cw*0602 binding. The uptake of MBP by B cells and the presentation of MBP-derive peptides to T helper (Th) cells by B cells may be promoted by the formation of complement (C) activating immune complexes (ICs) between MBP and natural autoantibodies in healthy individuals and disease-associated anti-MBP antibodies in MS patients, respectively. While MBP did not induce measurable proliferation of B cells nor CD4 þ T cells, we observed the production of TNF-a, IFN-g and IL-10 by PBMC in response to incubation with MBP in the presence of sera from healthy controls as well as sera from MS patients. In conclusion, the results of this study suggest an involvement of the ASMase in the activation, expansion or maturation of virus-specific CD8 þ T cells during the acute infection of mice with the LCM virus. doi = 10.1111/j.0300-9475.2004.01423ab.x id = cord-256837-100ir651 author = Smith, Steven B. title = Identification of Common Biological Pathways and Drug Targets Across Multiple Respiratory Viruses Based on Human Host Gene Expression Analysis date = 2012-03-14 keywords = Parkin; RSV; TNF; figure; gene; pathway; virus summary = Several recent studies have generated multiple mRNA microarray gene expression datasets derived from experiments involving the infection of human cell-lines or animal models with one or more of the major respiratory viruses [21] [22] [23] . Through a systematic analysis of these respiratory virus-human host gene expression datasets, we determined common sets of genes and pathways involved in host responses to viral infections. A total of seven different respiratory viruses were analyzed, represented by fifteen unique Gene Expression Omnibus (GEO) datasets (indicated by GEO Series or GSE accession numbers), nine different human cell types, and seven different array platforms for a total of 28 unique comparisons. This assumption is based on the occurrence of genes that are differentially expressed in infection models for at least five of the seven respiratory viruses, have involvement in a number of relevant pathways related to host immune response, and encode for known drug targets. doi = 10.1371/journal.pone.0033174 id = cord-323553-bukm9m9q author = Song, Woo-Jin title = Canine adipose tissue-derived mesenchymal stem cells pre-treated with TNF-alpha enhance immunomodulatory effects in inflammatory bowel disease in mice date = 2019-08-31 keywords = IBD; TNF; TSG-6 summary = title: Canine adipose tissue-derived mesenchymal stem cells pre-treated with TNF-alpha enhance immunomodulatory effects in inflammatory bowel disease in mice Mesenchymal stem cells (MSCs), which release immunomodulatory factors such as tumor necrosis factor-α (TNF-α)-induced gene/protein 6 (TSG-6) and prostaglandin E2 (PGE2), have been suggested as an alternative therapeutic option for IBD treatment in veterinary medicine. (C) Canine adipose tissue-derived mesenchymal stem cells (cAT-MSCs) stimulated with TNF-α released higher concentrations of immunomodulatory factors such as TSG-6 and PGE2 compared to levels released by naive cAT-MSCs. Results are shown as the mean ± standard deviation of three independent experiments. Canine adipose tissue-derived mesenchymal stem cells (cAT-MSCs) stimulated with TNF-α showed enhanced therapeutic effects on mice with dextran sodium sulfate (DSS)-induced colitis. Canine adipose tissue-derived mesenchymal stem cells (cAT-MSCs) stimulated with TNF-α showed enhanced therapeutic effects on mice with dinitrobenzene sulfonic acid (DNBS)-induced colitis. doi = 10.1016/j.rvsc.2019.06.012 id = cord-000324-to4g9he9 author = Spentzas, Thomas title = Ketamine inhibits tumor necrosis factor secretion by RAW264.7 murine macrophages stimulated with antibiotic-exposed strains of community-associated, methicillin-resistant Staphylococcus aureus date = 2011-01-25 keywords = LAC; MRSA; NMDA; TNF summary = title: Ketamine inhibits tumor necrosis factor secretion by RAW264.7 murine macrophages stimulated with antibiotic-exposed strains of community-associated, methicillin-resistant Staphylococcus aureus In a sepsis simulation model, we tested whether the anesthetic ketamine inhibits the macrophage TNF response to antibiotic-exposed CA-MRSA bacteria via its antagonism of N-methyl-D-aspartate (NMDA) receptors. The NMDA inhibitors, MK-801 and APV, also suppressed macrophage TNF secretion after stimulation with either of the antibiotic-exposed CA-MRSA isolates, and the effect was not additive or synergistic with ketamine. The mechanisms responsible for the anti-inflammatory effects of ketamine are not known [22] [23] [24] [25] .The present study examined the hypothesis that ketamine could suppress macrophage TNF production in response to whole bacteria, in this case clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA). The addition of ketamine (100 μΜ) to macrophage cell cultures inhibited TNF secretion in response to vancomycin-or daptomycin-exposed CA-MRSA isolates ( Figure 2) . doi = 10.1186/1471-2172-12-11 id = cord-023419-lnmc6vv5 author = Steinhauer, C. title = High‐Throughput Proteomics on Antibody‐based Microarrays: the Importance of Probe and Surface Design date = 2008-06-28 keywords = CD8; IFN; IL-12; MBL; TNF; cell summary = doi = 10.1111/j.0300-9475.2004.01423ax.x id = cord-023374-87ob1exq author = Sukhija, S. title = Levels, Complement Activity and Polymorphisms of Mannan‐Binding Lectin in Patients of Bronchial Asthma with Allergic Rhinitis date = 2008-06-28 keywords = CD8; IFN; IL-12; MBL; TNF; cell summary = We demonstrate that Cw6 þ psoriasis patients had significant CD8 þ T-cell IFN-g responses to peptides from K17 and M6 protein selected on the basis of sequence homology and predicted HLA-Cw*0602 binding. The uptake of MBP by B cells and the presentation of MBP-derive peptides to T helper (Th) cells by B cells may be promoted by the formation of complement (C) activating immune complexes (ICs) between MBP and natural autoantibodies in healthy individuals and disease-associated anti-MBP antibodies in MS patients, respectively. While MBP did not induce measurable proliferation of B cells nor CD4 þ T cells, we observed the production of TNF-a, IFN-g and IL-10 by PBMC in response to incubation with MBP in the presence of sera from healthy controls as well as sera from MS patients. In conclusion, the results of this study suggest an involvement of the ASMase in the activation, expansion or maturation of virus-specific CD8 þ T cells during the acute infection of mice with the LCM virus. doi = 10.1111/j.0300-9475.2004.01423ai.x id = cord-279498-ez3yq7xi author = Suzumura, Akio title = Immune Response in the Brain: Glial Response and Cytokine Production date = 2008-12-31 keywords = MHC; TNF summary = Cytokines such as interferon (IFN)-γ, tumor necrosis factor (TNF)-α, and interleukin (IL)-3 induce class I major histocompatibility complex (MHC) antigen expression on neural cells. In the brains of experimental allergic encephalomyelitis (EAE), microglia near the infiltrating T cells are reported to be class II MHC antigen-positive [6] [7] [8] , suggesting that a T cell-derived cytokine, most probably IFN-g, can induce class II MHC antigen expression in vivo as well. Since the BBB is not damaged in this experimental condition and since there is no definitive evidence that neural cells produce INF-g in the CNS, it is unlikely that IFN-g is responsible for the induction of class II MHC antigen expression in this model. In contrast to IL-3, granulocyte-macrophage colony-stimulating factor (GM-CSF) downregulates IFN-g-induced class II MHC antigen expression in microglia. IL-10 suppresses cytokine production and IFN-g-induced class II MHC antigen expression in microglia, but does not suppress the proliferation or the activation of lysosomal enzymes in microglia [18] . doi = 10.1016/s1567-7443(07)10014-4 id = cord-023421-1d1gf7az author = Sønder, S. U. S. title = Monitoring Patients Treated with Type 1 Interferons: Antiviral versus MxA Induction Assays date = 2008-06-28 keywords = CD8; IFN; IL-12; MBL; TNF; cell summary = We demonstrate that Cw6 þ psoriasis patients had significant CD8 þ T-cell IFN-g responses to peptides from K17 and M6 protein selected on the basis of sequence homology and predicted HLA-Cw*0602 binding. The uptake of MBP by B cells and the presentation of MBP-derive peptides to T helper (Th) cells by B cells may be promoted by the formation of complement (C) activating immune complexes (ICs) between MBP and natural autoantibodies in healthy individuals and disease-associated anti-MBP antibodies in MS patients, respectively. While MBP did not induce measurable proliferation of B cells nor CD4 þ T cells, we observed the production of TNF-a, IFN-g and IL-10 by PBMC in response to incubation with MBP in the presence of sera from healthy controls as well as sera from MS patients. In conclusion, the results of this study suggest an involvement of the ASMase in the activation, expansion or maturation of virus-specific CD8 þ T cells during the acute infection of mice with the LCM virus. doi = 10.1111/j.0300-9475.2004.01423bb.x id = cord-353887-f4yd7guj author = Tang, Yujun title = Cytokine Storm in COVID-19: The Current Evidence and Treatment Strategies date = 2020-07-10 keywords = COVID-19; IL-6; SARS; TNF; cell; clinical; cytokine summary = Besides, corticosteroids, programmed cell death protein (PD)-1/PD-L1 checkpoint inhibition, cytokine-adsorption devices, intravenous immunoglobulin, and antimalarial agents could be potentially useful and reliable approaches to counteract cytokine storm in COVID-19 patients. In this review, we referred COVID-19 associated cytokine storm as the patients who are severely ill along with a high concentration of pro-inflammatory cytokines. The innate and adaptive immune responses activated by SARS-CoV-2 infection lead to uncontrolled inflammatory responses and ultimately cause the cytokine storm (14) . MERS-CoV infects the cells mentioned above to induce delayed (but increased) levels of pro-inflammatory cytokines (e.g., IL-2) and chemokines (e.g., CCL2, CCL3) (27, 30) . Although SARS-CoV is abortive in macrophages and DCs, the virus induces an increase in levels of pro-inflammatory cytokines and chemokines (31, 32) . A comment and a meta-analysis, which mainly bases on the evidence of SARS and MERS (64, 65) , stated that corticosteroid would increase mortality and delayed clearance of viral in coronavirus infection diseases. doi = 10.3389/fimmu.2020.01708 id = cord-023928-9a1w174h author = Thomas, Neal J. title = Genetic Predisposition to Critical Illness in the Pediatric Intensive Care Unit date = 2011-12-16 keywords = ALI; TNF; dna; gene; genetic summary = authors: Thomas, Neal J.; Dahmer, Mary K.; Quasney, Michael W. Examples of the infl uence of genetic variations in proteins involved in recognition of pathogens on the severity of infections include polymorphisms in the genes coding for mannose binding Individual variability in the susceptibility to and outcome from critical care diseases has long been observed, and advances in genomic medicine now gives an opportunity to understand these differences. doi = 10.1007/978-0-85729-923-9_11 id = cord-023391-bq5w3jk9 author = Utermöhlen, O. title = Delayed Elimination of the LCM Virus from Acid Sphingomyelinase‐Deficient Mice due to Reduced Expansion of Virus‐Specific CD8(+) T Lymphocytes date = 2008-06-28 keywords = CD8; IFN; IL-12; MBL; TNF; cell summary = We demonstrate that Cw6 þ psoriasis patients had significant CD8 þ T-cell IFN-g responses to peptides from K17 and M6 protein selected on the basis of sequence homology and predicted HLA-Cw*0602 binding. The uptake of MBP by B cells and the presentation of MBP-derive peptides to T helper (Th) cells by B cells may be promoted by the formation of complement (C) activating immune complexes (ICs) between MBP and natural autoantibodies in healthy individuals and disease-associated anti-MBP antibodies in MS patients, respectively. While MBP did not induce measurable proliferation of B cells nor CD4 þ T cells, we observed the production of TNF-a, IFN-g and IL-10 by PBMC in response to incubation with MBP in the presence of sera from healthy controls as well as sera from MS patients. In conclusion, the results of this study suggest an involvement of the ASMase in the activation, expansion or maturation of virus-specific CD8 þ T cells during the acute infection of mice with the LCM virus. doi = 10.1111/j.0300-9475.2004.01423l.x id = cord-259586-kep2dgaw author = Van Reeth, Kristien title = In vivo studies on cytokine involvement during acute viral respiratory disease of swine: troublesome but rewarding date = 2002-09-10 keywords = IL-1; IL-6; TNF summary = This review concentrates on in vivo studies of cytokine involvement in infectious respiratory diseases of swine, with an emphasis on viral infections. In the authors'' laboratory, studies were undertaken to investigate the relationship between viral respiratory disease and bioactive lung lavage levels of IFN-α, TNF-α, IL-1 and IL-6. We have previously demonstrated different cytokine pro-®les in BAL¯uids of gnotobiotic pigs infected with porcine respiratory coronavirus (PRCV), porcine reproductive and respiratory syndrome virus (PRRSV) or swine in¯uenza virus (SIV) (Van Reeth et al., 1999) . In an attempt to study interactions between respiratory viruses and secondary agents in a reproducible way, we have performed subsequent inoculations of pigs with either PRCV or PRRSV followed by bacterial lipopolysaccharide (LPS). Prior infection with PRCV truly potentiated the cytokine response to LPS, with 10±100 times higher titres of TNF-a, IL-1 and IL-6 than after the respective single inoculations. Differential production of proin¯ammatory cytokines in the pig lung during different respiratory virus infections: correlations with pathogenicity doi = 10.1016/s0165-2427(02)00047-8 id = cord-341667-ayl71jpc author = Van Reeth, Kristien title = Bronchoalveolar Interferon-α, Tumor Necrosis Factor-α, Interleukin-1, and Inflammation during Acute Influenza in Pigs: A Possible Model for Humans? date = 1998-04-17 keywords = IL-1; TNF summary = Biologically active interferon-a, tumor necrosis factor-a (TNF-a), and interleukin-1 (IL-1) were detected in bronchoalveolar lavage (BAL) fluids of 3-week-old cesarian-derived colostrum-deprived pigs inoculated with H1N1 influenza virus. Biologically active interferon-a, tumor necrosis factor-a (TNF-a), and interleukin-1 (IL-1) were detected in bronchoalveolar lavage (BAL) fluids of 3-week-old cesarian-derived colostrum-deprived pigs inoculated with H1N1 influenza virus. Levels of the three cytokines were significantly higher 18 -24 h after inoculation than at 48 -72 h after inoculation (P õ Clinical responses, influenza virus titers, BAL cell numbers, percentage of neutrophils, and cytokine titers of individual pigs .016 for all three cytokines). On histopathology, bronchi/bronchioli and, to a lesser degree, alveoli showed epithelial necrosis and To our knowledge, this is the first demonstration of influenza virus -induced TNF-a and IL-1 in BAL fluids of a natural virus massive neutrophil infiltration at 18 -24 h after inoculation. doi = 10.1086/517398 id = cord-007621-rapinodd author = Vidovic, Maria title = Induction and regulation of class II major histocompatibility complex mRNA expression in astrocytes by interferon-γ and tumor necrosis factor-α date = 2002-11-13 keywords = IFN; MHC; RNA; TNF summary = Previous data from this laboratory had shown that the cytokine tumor necrosis factor-α (TNF-α) enhances IFN-γ-mediated class II antigen expression on astrocytes. To determine the steady-state level of mRNA for class II, Northern blot analysis was performed using a eDNA probe for murine class Ii genes (E-a), with total RNA isolated from cultured astrocytes. The duration of protein synthesis required to allow expression of the class II MHC gene in astrocytes was examined in cells that were pretreated with IFN-y or IFN-7/TNF-a for different lengths of time prior to the addition of CHX. In this study we have shown that primary neonatal rat astrocytes, upon stimulation with IFN-~,, express mRNA transcripts for class II MHC genes, and that TNF-a enhances the expression of IFN-~,-induced class II mRNA. The expression of class II mRNA was completely inhibited when CHX was included with IFN-~, and IFN-''t/TNF-~ treatment, indicating that newly synthesized protein is required for astrocyte class II MHC gene expression. doi = 10.1016/0165-5728(90)90103-t id = cord-023417-by18aczt author = Vilhelmsson, M. title = The Malassezia sympodialis Allergen Mala s 11 with Sequence Similarity to Manganese Superoxide Dismutase Induces Maturation and Production of Inflammatory Cytokines in Human Dendritic Cells date = 2008-06-28 keywords = CD8; IFN; IL-12; MBL; TNF; cell summary = doi = 10.1111/j.0300-9475.2004.01423ae.x id = cord-005872-w1x1i0im author = Volk, T. title = Endothelium function in sepsis date = 2000 keywords = HUVEC; LPS; TNF; cell; endothelial; human; sepsis summary = Defects in endothelium dependent vasoregulation in animal models are well known and again human studies are largely missing.¶An imbalanced production of reactive oxygen species including nitric oxide has been found to be involved in all endothelial functions and may provide a common link which at present can be supported only in animal studies. S. aureus has been reported to directly infect human umbilical vein endothelial cells (HUVEC) thereby inducing secretion of cytokines and functional upregulation of adhesion molecules [2] . Infection and activation of endothelial cells by Listeria monocytogenes is believed to be a critical component of the pathogenesis of this disease and includes ceramide generation, transcription factor activation and increases in adhesion molecule expression on HUVEC [11] . E-selectin expression in human endothelial cells by TNF-alpha-induced oxidant generation and NF-kappaB activation doi = 10.1007/s000110050579 id = cord-022353-q2k2krnm author = W. Quimby, Fred title = Clinical Chemistry of the Laboratory Mouse date = 2007-09-02 keywords = C57BL/6; ELISA; HDL; IL-1; IL-6; Quimby; TNF; cell; level; mouse; receptor; serum summary = Assessment of long-term average blood glucose levels in mice is also available by RIAs measuring glycosylated hemoglobin and glycosylated serum proteins (collectively known as fructosamines) (Gould et al. Leptin resistance, a common feature of obesity in mice and humans, has also been shown to result, in part, from the shedding of membrane-bound hepatic leptin receptors into the plasma, where soluble receptors modulate circulating leptin levels and possibly its biologic activity (Cohen et al. d. OTHER ANALYTES ASSOCIATED WITH LIPID METABOLISM AND ATHEROSCLEROSIS IN MICE ELISA kits are commercially available for the quantitation of many mouse coagulation proteins including: fibrinogen, factor VII, d-dimer, tissue factor, and von Willebrand''s factor antigen. The ability of the first component of complement, C1, to bind specific sites on the heavy chain of mouse IgG2b and activate a sequence of reactions leading to production of a molecular unit capable of lysing a target cell membrane has established the complement system as the primary mediator of antibody-antigen reactions. doi = 10.1016/b978-012369454-6/50060-1 id = cord-291076-p350i54m author = Wang, Renxi title = The role of C5a in acute lung injury induced by highly pathogenic viral infections date = 2015-05-06 keywords = ALI; H5N1; SARS; TNF summary = Unregulated complement activation is likely to play a crucial role in the pathogenesis of acute lung injury (ALI) induced by highly pathogenic virus including influenza A viruses H5N1, H7N9, and severe acute respiratory syndrome (SARS) coronavirus. [1] [2] [3] In addition, the complement system has been implicated in the development of acute lung diseases induced by highly pathogenic viruses including influenza A virus H1N1, 4 H5N1, 5 H7N9, 6 severe acute respiratory syndrome coronavirus (SARS-Cov), 7 Middle East respiratory syndrome coronavirus (MERS-Cov). C5a-mediated release of reactive oxygen species C5a is a strong chemoattractant for neutrophils and monocytes; it then activates these cells to generate oxidative burst with release of 10 A study demonstrated that ROS are primary pathogenic molecules in pneumonia from mice infected with influenza virus. Inhibition of Complement Activation Alleviates Acute Lung Injury Induced by Highly Pathogenic Avian Influenza H5N1 Virus Infection doi = 10.1038/emi.2015.28 id = cord-346669-7n75m669 author = Wang, Shixin title = Roles of TNF-α gene polymorphisms in the occurrence and progress of SARS-Cov infection: A case-control study date = 2008-02-29 keywords = SARS; TNF summary = This study was to investigate the relationship between tumor necrosis factor (TNF)-α gene polymorphisms with the occurrence of SARS-CoV infection and its role in prognosis of patients with lung interstitial fibrosis and femoral head osteonecrosis. METHODS: The association between genetic polymorphisms of TNF-α gene and susceptibility to severe acute respiratory syndromes (SARS) was conducted in a hospital-based case-control study including 75 SARS patients, 41 health care workers and 92 healthy controls. Relationships of TNF-α gene polymorphisms with interstitial lung fibrosis and femoral head osteonecrosis were carried out in two case-case studies in discharged SARS patients. In this paper, we aimed to study whether polymorphisms in TNF-α promoter region were associated with SARS-CoV infection, development, and progression of interstitial lung fibrosis and femoral head necrosis in cure SARS patients. Considered that the progression of interstitial lung fibrosis or femoral head necrosis may be affected by hormone therapy, hormone using dosage, method and lasting period were considered in this study when analyzing the associations between gene polymorphisms with disease. doi = 10.1186/1471-2334-8-27 id = cord-306983-6w2fvtfy author = Wang, Siye title = Influenza Virus—Cytokine-Protease Cycle in the Pathogenesis of Vascular Hyperpermeability in Severe Influenza date = 2010-10-01 keywords = TNF; figure; influenza; virus summary = Influenza A virus infection resulted in significant increases in TNF-α, IL-6, IL-1β, viral hemagglutininprocessing protease trypsin levels, and viral replication with vascular hyperpermeability in lung and brain in the first 6 days of infection. The present study reports several new observations: (1) proinflammatory cytokines, TNF-a, IL-1b, and IL-6, when upregulated by influenza A virus infection, induce trypsin expression in various organs and human endothelial cells; (2) the upregulated trypsin induces [Ca 2+ ] i mobilization via activation of the PAR-2, followed by loss of zonula occludens-1 and vascular hyperpermeability; (3) inhibitors of NF-kB and activator protein 1 effectively suppress the upregulation of proinflammatory cytokines and trypsin and improve the survival rates of infected mice. The present results allow us to propose a new mechanism of junctional permeability regulation: upregulated trypsin by influenza A virus and/or proinflammatory cytokines induces increase in [Ca 2+ ] i and loss of zonula occludens-1 in endothelial cells via PAR-2 signaling. doi = 10.1086/656044 id = cord-336432-tu00gffr author = Wang, Zhiyu title = Small molecule therapeutics for COVID-19: repurposing of inhaled furosemide date = 2020-07-07 keywords = COVID-19; IL-6; LPS; TNF; inflammatory summary = In this study, a library of small molecules endogenous to the human body was assembled, subjected to in silico molecular docking simulations and a focused in vitro screen to identify anti-pro-inflammatory activity via interleukin inhibition. To pre-clinically evaluate furosemide as a putative COVID-19 therapeutic, we studied its anti-inflammatory activity on RAW264.7, THP-1 and SIM-A9 cell lines stimulated by lipopolysaccharide (LPS). Accordingly, we set out to identify a small molecule with the following properties: broad-spectrum anti-inflammatory mechanism of action targeting cytokines of innate immunity; low toxicity and excellent safety profile; chemically stable; easily stored and administered; able to be rapidly adopted in clinical settings worldwide; and, widespread availability with inexpensive and efficient means of production. A library of 1,136 small molecules endogenous to the human body was assembled, subjected to in silico molecular docking simulations and a focused in vitro screen to identify anti-pro-inflammatory activity via interleukin inhibition. doi = 10.7717/peerj.9533 id = cord-272237-gnno6elo author = Wang, Ziran title = A Wearable and Deformable Graphene-Based Affinity Nanosensor for Monitoring of Cytokines in Biofluids date = 2020-07-31 keywords = IFN; TNF; figure summary = A wearable and deformable graphene-based field-effect transistor biosensor is presented that uses aptamer-modified graphene as the conducting channel, which is capable of the sensitive, consistent and time-resolved detection of cytokines in human biofluids. Based on an ultrathin substrate, the biosensor offers a high level of mechanical durability and consistent sensing responses, while conforming to non-planar surfaces such as the human body and withstanding large deformations (e.g., bending and stretching). Moreover, Tween 80 is used to modify the graphene surface to effectively suppress nonspecific adsorption, thus enabling the biosensor to detect cytokines (TNF-α and IFN-γ, significant inflammatory cytokines, were used as representatives) in artificial tears (used as a biofluid representative). Moreover, Tween 80 is used to modify the graphene surface to effectively suppress nonspecific adsorption, thus enabling the biosensor to detect cytokines (TNF-α and IFN-γ, significant inflammatory cytokines, were used as representatives) in artificial tears (used as a biofluid representative). doi = 10.3390/nano10081503 id = cord-023389-ilrp8vb7 author = Wefer, J. title = Protective DNA Vaccination Against MOG(91‐108)‐Induced Experimental Autoimmune Encephalomyelitis Involves Induction of IFNβ date = 2008-06-28 keywords = CD8; IFN; IL-12; MBL; TNF; cell; dna summary = We demonstrate that Cw6 þ psoriasis patients had significant CD8 þ T-cell IFN-g responses to peptides from K17 and M6 protein selected on the basis of sequence homology and predicted HLA-Cw*0602 binding. The uptake of MBP by B cells and the presentation of MBP-derive peptides to T helper (Th) cells by B cells may be promoted by the formation of complement (C) activating immune complexes (ICs) between MBP and natural autoantibodies in healthy individuals and disease-associated anti-MBP antibodies in MS patients, respectively. While MBP did not induce measurable proliferation of B cells nor CD4 þ T cells, we observed the production of TNF-a, IFN-g and IL-10 by PBMC in response to incubation with MBP in the presence of sera from healthy controls as well as sera from MS patients. In conclusion, the results of this study suggest an involvement of the ASMase in the activation, expansion or maturation of virus-specific CD8 þ T cells during the acute infection of mice with the LCM virus. doi = 10.1111/j.0300-9475.2004.01423j.x id = cord-351387-i0zamkpd author = Witte, Katrin title = The Pelargonium sidoides Extract EPs 7630 Drives the Innate Immune Defense by Activating Selected MAP Kinase Pathways in Human Monocytes date = 2015-09-25 keywords = IL-10; IL-6; Pelargonium; TNF summary = In summary, we demonstrate that EPs 7630 activates human monocytes, induces MAP kinase-dependent pro-inflammatory cytokines in these cells, and specifically modulates their production capacity of mediators known to lead to an increase of acute phase protein production in the liver, neutrophil generation in the bone marrow, and the generation of adaptive Th17 and Th22 cells. In the first setting, PBMCs were stimulated with EPs 7630 (3 and 30 μg/ml), Escherichia coli 0127:B8 lipopolysaccharide (TLR4 ligand; 100 ng/ml; Sigma-Aldrich), polyinosinic-polycytidylic acid [poly (I:C); 10 μg/ml; Sigma-Aldrich], a cytokine mixture of IL-1β, IL-2 and IL-12 (10 ng/ml each; R&D systems), anti-CD3 (Orthoclone; Cilag) and anti-CD28 (R&D systems) monoclonal antibodies (1 μg/ml each), or were left without specific treatment (0.1% ethanol as solvent control) for 4 and 24 h, before cell culture supernatant was recovered for ELISA cytokine production analysis. Our data show that EPs 7630 strongly and dose-dependently induced the production of the pro-inflammatory cytokines TNF-α and IL-6 in human blood immune cells. doi = 10.1371/journal.pone.0138075 id = cord-348391-xytmq2f2 author = Wyganowska-Swiatkowska, Marzena title = Influence of Herbal Medicines on HMGB1 Release, SARS-CoV-2 Viral Attachment, Acute Respiratory Failure, and Sepsis. A Literature Review date = 2020-06-30 keywords = HMGB1; IL-6; LPS; SARS; TNF; extract; inflammatory summary = While long term proteinase and ACE-2 inhibition could be detrimental to cellular function and bodily homeostasis, targeted treatment partially reducing the effectiveness of coronavirus S protein attachment to the ACE2 or to the priming proteinase could have the potential to drop the SARS-CoV-2 viral load before a state of septic shock is reached at the peak of infection. Aspalathin and nothofagin extracted from Rooibos have been shown to effectively inhibit LPS-induced release of HMGB1, and suppressed HMGB1-mediated septic responses, such as hyperpermeability, adhesion and migration of leukocytes, and expression of cell adhesion molecules [124] . The effect and mechanism of salidroside on sepsis-induced acute lung injury is mediated by the inhibition of inflammatory responses and HMGB1 production in bacterial LPS-treated macrophages and mice. Study has shown that pelargonidin (PEL) had effectively inhibited LPS-induced release of HMGB1 and suppressed HMGB1-mediated septic responses, such as hyperpermeability, adhesion and migration of leukocytes, and expression of cell adhesion molecules. doi = 10.3390/ijms21134639 id = cord-007858-1ijxilpb author = Xu, G.L. title = Attenuation of acute lung injury in mice by oxymatrine is associated with inhibition of phosphorylated p38 mitogen-activated protein kinase date = 2005-04-08 keywords = ALI; MAP; TNF- summary = Furthermore, pretreatment with oxymatrine significantly alleviated oleic acid-induced lung injury accompanied by reduction of lung index and wet-to-dry weight ratio, decreases in serum TNF-α level and inhibition of phosphorylated p38 MAPK. These findings suggest that oxymatrine has a beneficial effect on acute lung injury induced by oleic acid in mice and may inhibit the production of proinflammatory cytokine, TNF-α, by means of the inhibition of p38 MAPK. Light microscopic findings in the lung at 6 h after oleic acid injection demonstrated a marked lung injury resembling those seen in lung of patients with ALI/ARDS, represented by prominent atelectasis, intraalveolar and interstitial patchy hemorrhage, edema, thickened alveolar septum, formation of hyaline membranes and the existence of inflammatory cells in alveolar spaces (Fig. 1A) , which were not observed in the control group (Fig. 1B) . Effect of oxymatrine on serum TNF-␣ level in mice with lung injury induced by oleic acid. doi = 10.1016/j.jep.2005.01.026 id = cord-002326-3qb1ym4w author = Yang, Runkuan title = Ethyl pyruvate is a novel anti-inflammatory agent to treat multiple inflammatory organ injuries date = 2016-12-03 keywords = HMGB1; SAP; TNF summary = EP (40 mg/kg) was intraperitoneally injected every 6 h for 48 h)] significantly ameliorates pancreatic injury and necrosis [4, 6] ; EP therapy also markedly reduces pancreatic expression of TNF-α, IL-6, HMGB1 and NF-kB DNA binding [4, 6] ; treatment with EP reduces the number of inflammatory cell infiltration and decreases the pancreatic level of lipid peroxidation, which is a parameter of ROS [4] . Hepatic I/R induces significantly increased hepatic expression of TNF-α, IL-6, HMGB1 and NF-kB activation, and hepatic I/R also induces markedly increased hepatic expression of Bcl-2, Bax, Beclin-1 and LC3, which play an important role in the regulation of intrinsic pathway of apoptosis and autophagy, all of these changes are significantly reduced by EP treatment (1 h before the ischemia procedure, a single dose of EP was intraperitoneally injected to animals in the 20 mg/kg group, the 40 mg/kg group and the 80 mg/kg group, liver tissue samples were obtained 4 h, 6 h and 16 h after I/R), suggesting that EP ameliorates hepatic I/R injury via its antiinflammatory and its anti-apoptosis effect. doi = 10.1186/s12950-016-0144-1 id = cord-307813-elom30nx author = Yip, Tsz-Fung title = Advancements in Host-Based Interventions for Influenza Treatment date = 2018-07-10 keywords = IAV; IFN; TNF; cell; infection; influenza; viral; virus summary = Besides controlling virus replication, potential targets for drug development include controlling virus-induced host immune responses such as the recently suggested involvement of innate lymphoid cells and NADPH oxidases in influenza virus pathogenesis and immune cell metabolism. Besides controlling virus replication, potential targets for drug development include controlling virus-induced host immune responses such as the recently suggested involvement of innate lymphoid cells and NADPH oxidases in influenza virus pathogenesis and immune cell metabolism. A recent study using RNAi also demonstrated that cholesterol homeostasis can be regulated via acid phosphatase 2 (ACP2)-mediated Niemann-Pick C2 activity and impaired the membrane fusion of IAV and influenza B virus (IBV) (52) , further suggesting the importance of controlling cholesterol homeostasis in the release of viral genome to cytoplasm. Furthermore, FPR2 antagonists have been described to possess antiviral activity against not only IAV but also IBV infection (111) , promoting the idea that antagonizing FPR2 to suppress Raf/MEK/ERK signaling cascade could potentially be a novel approach for the treatment of a broad spectrum of influenza viruses. doi = 10.3389/fimmu.2018.01547 id = cord-302258-derq9b27 author = Zhang, Hui title = Effects of ubiquitin-proteasome inhibitor on the expression levels of TNF-α and TGF-β1 in mice with viral myocarditis date = 2019-08-14 keywords = TGF; TNF; VMC summary = Effects of ubiquitin-proteasome system (UPS) inhibitor MG-132 on the expression levels of tumor necrosis factor-α (TNF-α) and transforming growth factor-β1 (TGF-β1) in mice with viral myocarditis were investigated to analyze the correlation of myocardial tissue score of mice between TNF-α and TGF-β1. Mortality rates of each group were recorded and compared on day 8 of modeling, and heart specimens from the remaining mice were histopathologically examined and the expression of mRNA and protein of TNF-α and TGF-β1 in myocardial tissues were detected by western blot analysis. The expression levels of myocardial histopathological scores, mRNA and protein of TNF-α and TGF-β1 in the blank and control group were significantly lower than those in the VMC and the MG-132 group. At present, few studies have reported the role of UPS in the inflammatory reaction of VMC, so we explored the effect of ubiquitin-proteasome inhibitor MG-23 on the expression levels of serum TNF-α and TGF-β1 in CVB mice, in order to understand the inflammatory mechanism of VMC. doi = 10.3892/etm.2019.7895 id = cord-004879-pgyzluwp author = nan title = Programmed cell death date = 1994 keywords = ATP; Basel; Bern; Drosophila; Institut; Lausanne; NMDA; PCR; PKC; RNA; Switzerland; TNF; University; acid; activity; cell; dna; expression; gene; high; human; increase; level; mouse; protein; receptor; result; sequence; study; type summary = Furthermore kinetic experiments after complementation of HIV=RT p66 with KIV-RT pSl indicated that HIV-RT pSl can restore rate and extent of strand displacement activity by HIV-RT p66 compared to the HIV-RT heterodimer D66/D51, suggesting a function of the 51 kDa polypeptide, The mouse mammary tumor virus proviral DNA contains an open reading frame in the 3'' long terminal repeat which can code for a 36 kDa polypeptide with a putative transmembrane sequence and five N-linked glycosylation sites. To this end we used constructs encoding the c-fos (and c-jun) genes fused to the hormone-binding domain of the human estrogen receptor, designated c-FosER (and c-JunER), We could show that short-term activation (30 mins.) of c-FosER by estradiole (E2) led to the disruption of epithelial cell polarity within 24 hours, as characterized by the expression of apical and basolateral marker proteins. doi = 10.1007/bf02033112 id = cord-005814-ak5pq312 author = nan title = 8th European Congress of Intensive Care Medicine Athens - Greece, October 18–22, 1995 Abstracts date = 1995 keywords = AMI; APACHE; ARDS; ARF; COPD; CPB; CPR; CVP; Care; ECG; ECMO; Group; H20; Hospital; ICP; ICU; III; IL-6; Intensive; January; LPS; MOF; PSV; SAPS; TNF; Unit; University; acute; blood; cardiac; change; conclusion; control; day; effect; failure; follow; high; hour; increase; level; mean; measure; method; mortality; objective; patient; peep; pressure; pulmonary; respiratory; result; study; treatment; value summary = Results: In 5 patients with treated SS, 16 tests were performed (VL n=8; Dobu n=4; NA n=4 Method: Septic shock was defined as severe sepsis with either persistent hypotension (mean arterial pressure; MAP<70 mmHg) or the requirement for a noradrenaline (NA) infusion ~> 0.1 ~g/kg/min with a MAP _< 90mmHg. Cardiovascular support was limited to NA + dobutamine (DB), 546C88 was administered for up to 8 h at a fixed dose-rate of either i, 2.5, 5, 10 or 20 mg/kg/h iv. Methods: Fourteen cases were s~udied,their gestational age ranged from(27-32)ws.Continnous positive air way pressure was applied to six cases at Peep level from (3-6)cm H2o through nasal pronge,(group I),the other 8 cases were managed as routine,(group II).Blood gases, TcPO2,TcCo2,resp.rate,depth and pattern were monitored for assessment of tissue Oxygenation and ventilation, Results: Our rasults showed that early application of CPAP improve ventilation among (83.3%)of cases,while (16.7%)of cases need IMV.The cases of group II need IMV among (75%)of the studied cases during the second or the third day of life. doi = 10.1007/bf02426401 id = cord-006230-xta38e7j author = nan title = Deutsche Gesellschaft für Experimentelle und Klinische Pharmakologie und Toxikologie e.V. date = 2012-02-22 keywords = ATP; ERK; Germany; IL-6; Institut; LPS; NDPK; PCR; PKA; Pharmakologie; RKIP; ROS; Rac1; TNF; TRPC6; TRPM3; TTC; Toxikologie; Universität; V79; activity; cell; concentration; dna; effect; expression; gene; human; increase; level; mouse; protein; receptor; result; study; western summary = Here, we will present our analysis of Ca 2+ signaling following stimulation of the FcεRI receptor and application of secretagogues that are supposed to affect Ca 2+ -dependent mast cell activation such as adenosine, endothelin-1, substance P and compound 48/80 in BMMCs and PMCs derived from mouse lines with inactivation of TRPC1, TRPC3, TRPC4, TRPC5 or TRPC6 since specific antagonists are still lacking for these TRP channels. These data indicate that increased PP2A activity is associated with modified gene expression in TG hearts possibly affecting stress response and regulation of cell signalling. As demonstrated by qPCR and Western blot experiments, mesangial cells showed a marked time-and dose-dependent upregulation of CSE mRNA and protein levels after treatment with platelet-derived growth factor (PDGF-BB). The transcription factor cAMP response element (CRE)-binding protein (CREB) plays a critical role in regulating gene expression in response to activation of the cAMPdependent signaling pathway, which is implicated in the pathophysiology of heart failure. doi = 10.1007/s00210-012-0736-0 id = cord-006444-eq56zhtd author = nan title = Abstracts of oral presentations and posters date = 1993 keywords = AML; CD34; CFU; CSF; IFN; IL-1; IL-2; IL-3; IL-4; IL-6; PBPC; SCF; TNF; cell; day; patient summary = The results from ongoing preclinical studies continue to confirm the broad spectrum of biological activities possessed by rhiL-1 1 in vitro and suggest this cytokine may be an effective agent in the treatment of myelosuppression associated with cancer chemotherapy and bone marrow transplantation. We performed a phase H trial to assess the ability of G-CSF -mobilized PBPC to rapidly and completely restore hemopeiesis after high dose chemotherapy in the absence of bone marrow infusions, with selection for PBPC-only infusions based on yield of granulocyte -macrophage colony -forming cells (GM-CFC) after G-CSF treatment. Our approach for high-dose (HD) chemotherapy is to first treat patients eligible for dose intensification with a standard dose chemotherapy (VIP: VP26 = etoposide: 500 mg/m 2, ifosfamide: 4 g/m 2, cis-platinum: 50 mg/m 2) followed by the application of colony stimulating factors (G-CSF, GM-CSF or IL-3 + GM-CSF) in order to combine a regimen with broad anti-tumor activity with the recruitment of peripheral blood progenitor cells (PBPCs). doi = 10.1007/bf01695978 id = cord-006828-i88on326 author = nan title = Abstracts DGRh-Kongress 2013 date = 2013-09-15 keywords = Background; CD4; ELISA; IFN; IL-6; MRI; MTX; Patienten; SLE; TNF; Therapie; arthritis; cell; der; die; disease; mit; patient; result; und summary = Comparing gene expression profiles of yellow fever immunized individuals and active SLE patients it was possible to identify a "common" and an "autoimmune-specific" IFN signature. The inflammatory and profibrotic effects upon Aab stimulation in vitro, and their associations with clinical findings suggest a role for autoantibody-mediated activation of immune cells mediated through the AT1R and ETAR in the pathogenesis or even the onset of the disease. This study was aimed to investigate the humoral and cellular immune response to VZV including assessment of IgG-anti-VZV avidity and VZV-specific reactivity of lymphocytes in RA (n=56) or JIA patients (n=75) on different treatments, including biologic agents, such as anti-tumor-necrosis-factor(TNF)-alpha or anti-interleukin-6 (IL-6) receptor inhibition (tocilizumab), compared to 37 healthy adults (HA) and 41 children (HC). Production of cytokines by B cells in response to TLR9 stimulation inversely correlates with disease activity in SLE-patients doi = 10.1007/s00393-013-1255-1 id = cord-015021-pol2qm74 author = nan title = Third International Congress on the Immune Consequences of Trauma, Shock and Sepsis —Mechanisms and Therapeutic Approaches date = 1994 keywords = APACHE; ARDS; CD14; CD4; CLP; CRP; CSF; ELISA; ICU; IFN; III; IL-1; IL-2; IL-4; IL-6; IL-8; LEH; LPS; MOF; PAF; PMN; SIRS; TNF; University; animal; blood; cell; control; cytokine; day; effect; endotoxin; factor; follow; group; high; increase; injury; level; method; mouse; patient; production; rat; release; response; result; sepsis; septic; shock; study; trauma summary = It is our current understanding that LPS is responsible for many of the pathophysiological events observed during gramnegative infections and that one of the major mechanisms leading to shock and death is the LPS-induced activation of macrophages resulting in the production and release of lipid and peptide mediators, among which tumor necrosis factor seems to be the most important. However plasma IL-6 estimation revealed a statistically significant reduction at 6 hours in tanrine-treated animals compared to glycino and TW controls ( Objective: To evaluate the effects of allogeneic blood transfusion, thermal injury and bacterial garage on interteukin 4 (IL-4), tumor necrosis factor alpha (TNF) production and host mortality and to study if the administration of thymopentth (THY) could affect these events. doi = 10.1007/bf02258437 id = cord-015147-h0o0yqv8 author = nan title = Oral Communications and Posters date = 2014-09-12 keywords = CIA; COX-2; Department; ELISA; IFN; IL-6; Institute; LPS; MIF; MPO; PAF; PCR; PGE2; TNF; University; cell; disease; effect; expression; increase; inflammation; inflammatory; level; model; mouse; response; result; study summary = Cyclooxygenases (COX) catalyze the first step in the synthesis of prostaglandins (PG) from arachidonic acid.COX-1 is constitutively expressed.The COX-2 gene is an immediate early-response gene that is induced by variety of mitogenic and inflammatory stimuli.Levels of COX-2 are increased in both inflamed and malignant tissues.In inflamed tissues, there is both pharmacological and genetic evidence that targeting COX-2 can either improve (e.g., osteoarthritis) or exacerbate symptoms (e.g., inflammatory bowel disease).Multiple lines of evidence suggest that COX-2 plays a significant role in carcinogenesis.The most specific data that support a cause-and effect relationship between COX-2 and tumorigenesis come from genetic studies.Overexpression of COX-2 has been observed to drive tumor formation whereas COX-2 deficiency protects against several tumor types.Selective COX-2 inhibitors protect against the formation and growth of experimental tumors.Moreover, selective COX-2 inhibitors are active in preventing colorectal adenomas in humans.Increased amounts of COX-2-derived PGE2 are found in both inflamed and neoplastic tissues.The fact that PGE2 can stimulate cell proliferation, inhibit apoptosis and induce angiogenesis fits with evidence that induction of COX-2 contributes to both wound healing and tumor growth.Taken together, it seems likely that COX-2 induction contributes to wound healing in response to injury but reduces the threshold for carcinogenesis. doi = 10.1007/bf03353884 id = cord-015394-uj7fe5y6 author = nan title = Scientific Abstracts date = 2008-12-23 keywords = ACTH; AEA; ANOVA; BMI; CRF; Center; ELISA; EOC; ERK; GDM; Gynecology; Hospital; IL-1; IL-6; IL-8; IUGR; IVF; LPS; Medical; Medicine; NIH; Netherlands; Obstetrics; P<0.05; PCOS; PCR; PPROM; RNA; Research; School; TNF; USA; University; VEGF; cell; conclusion; control; dna; expression; fetal; fsh; human; increase; level; maternal; method; objective; placental; pregnancy; result; study; western; woman summary = Studies involving immunohistochemical analysis of normal ovaries have shown that granulosa cells express significantly higher levels of the activator protein-1 (AP-1) transcription factor, cFos compared to theca cells, where cFos expression is virtually absent. Following acute hypoxia (0.5% O2) for one to six hours, RhoA mRNA, total protein and activation (RhoA-GTP) levels were analysed, using semi-quantitative PCRs and western blot, and compared to normoxic non-pregnant human uterine smooth muscle control cells. Since there is an urgent need for non-invasive methods for determination of fetal (F) and placental (P) function, this study was designed to evaluate the genes differently and commonly expressed in P tissue and leukocytes in maternal (M) and F circulation.Material and Methods. The current study: 1) localized IL-6 mRNA levels in preeclamptic versus normal decidual sections; 2) evaluated mechanisms regulating IL-6 synthesis by targeting intracellular signaling pathways with specific inhibitors; 3) identified potential IL-6 targets by immunolocalizing the IL-6 receptor (IL-6R) to specific cell types in placental bed biopsies. doi = 10.1177/19337191080150020102 id = cord-016168-3hyb9stq author = nan title = Pathogenesis of Fever date = 2009 keywords = IL-1; TNF; fever; heat summary = • Fever (pyrexia) is a regulated body temperature above the normal range occurring as a result of IL-1-mediated elevation of the hypothalamic set point. • Cytokines are proteins produced throughout the body, mainly by monocytes, macrophages, and T cells to regulate the immune responses within the body and control inflammatory and haematopoietic processes and may induce fever. • Pro-inflammatory cytokines (IL-1, IL-6, TNF-α, INF-γ, granulocyte-macrophage colony-stimulating factor, GM-CSF) are responsible for initiating an effective defense against exogenous organisms. Other mechanisms to initiate fever include the following: Some endotoxins, produced by bacteria, act directly on the hypothalamus to alter the set point. Mechanisms by which viruses may produce fever include direct invasion of macrophages, immunological reaction to viral components involving antibody formation, induction by INF, and necrosis of cells by viruses. Increased TNF production in Kawasaki disease may play a role in the immune activation and damage to vascular endothelial cells occurring in the disease. doi = 10.1007/978-3-540-78598-9_3 id = cord-022888-dnsdg04n author = nan title = Poster Sessions date = 2009-08-19 keywords = APC; BCR; CD14; CD4; CD8; CMV; CTL; EBV; ELISA; Germany; HCV; HIV; HLA; IBD; IFN; IL-10; IL-2; IL-4; IL-6; Immunology; Institute; LPS; MHC; NKT; PCR; RNA; SLE; TCR; TGF; TLR; TLR4; TNF; University; antigen; cell; dna; expression; immune; mouse; patient; protein; response; result; study; th1; th2 summary = Methods: Phospho-specific Western blot analyses were performed to verify the functionality of the different IFN-g pathway components, intra-and extracellular flow cytometry experiments were employed to determine the expression of antigen processing components and HLA class I cell surface antigens, quantitative real time-PCR experiments to confirm the absence of JAK2 and presence of pathway relevant molecules as well as, genomic PCR and chromosome typing technique to prove the deletion of JAK2. In order to accomplish these objectives we induced priming or tolerance of ovalbumin (OVA 323-339 peptide)-specific T cells from DO11.10 TCR transgenic mice in vitro or, following adoptive transfer of near physiologically relevant numbers of such cells into recipients, in vivo and correlated functional outcome (via proliferation and cytokine readout assays or antibody production) with E3 ubiquitin-protein ligases expression and the ubiquitination status of the TCR signalling machinery. doi = 10.1002/eji.200990224 id = cord-022940-atbjwpo5 author = nan title = Poster Sessions date = 2016-09-07 keywords = Akt; Ankara; Biology; Department; ELISA; Faculty; GSH; HCC; IL-6; IMA; Institute; Istanbul; MCF-7; MDA; MTT; P-02.08.5; P-09.04.4; PCR; PON1; RNA; ROS; Research; Russian; SOD; Sciences; TAS; TNF; TOS; Turkey; University; activity; analysis; cancer; cell; conclusion; control; dna; effect; expression; gene; group; high; increase; introduction; level; method; patient; protein; result; study; tissue; treatment; turkish; western summary = We have studied the effect of inhibition of IRE1 (inositol requiring enzyme 1), which is a central mediator of endoplasmic reticulum stress and controls cell proliferation and tumor growth, on hypoxic regulation of the expression of different proliferation related genes in U87 glioma cells. Transient inhibition of Akt and mTOR protein kinase activation in tumor cells followed by reactivation of signaling pathway did not result in a time-dependent difference on EGFR, HER2 and HER3 expression levels. In our study we aimed to determine cytotoxic effect of RES in K562 human CML cell line and to evaluate the expressions of miRNAs that are associated with genetics of leukemia after treatment with RES; to investigate target genes of miRNAs which show significant expression alterations and molecular mechanisms of RES treatment. doi = 10.1111/febs.13808 id = cord-023443-pvz7dll9 author = nan title = Abstracts for the Scandinavian Society for Immunology 35th Annual Meeting and 20th Summer School date = 2004-06-02 keywords = CD8; IFN; IL-12; MBL; TNF; cell summary = We demonstrate that Cw6 þ psoriasis patients had significant CD8 þ T-cell IFN-g responses to peptides from K17 and M6 protein selected on the basis of sequence homology and predicted HLA-Cw*0602 binding. The uptake of MBP by B cells and the presentation of MBP-derive peptides to T helper (Th) cells by B cells may be promoted by the formation of complement (C) activating immune complexes (ICs) between MBP and natural autoantibodies in healthy individuals and disease-associated anti-MBP antibodies in MS patients, respectively. While MBP did not induce measurable proliferation of B cells nor CD4 þ T cells, we observed the production of TNF-a, IFN-g and IL-10 by PBMC in response to incubation with MBP in the presence of sera from healthy controls as well as sera from MS patients. In conclusion, the results of this study suggest an involvement of the ASMase in the activation, expansion or maturation of virus-specific CD8 þ T cells during the acute infection of mice with the LCM virus. doi = 10.1111/j.1365-3083.2004.01423.x id = cord-034340-3ksfpaf7 author = nan title = Proceedings of the 26th European Paediatric Rheumatology Congress: part 2: Virtual. 23 - 26 September 2020 date = 2020-10-28 keywords = ANA; ESR; IVIG; JIA; MAS; MTX; SLE; TNF; arthritis; case; child; clinical; disease; introduction; patient; result; treatment; year summary = Objectives: The current study was undertaken to evaluate sociodemographic and sociocultural features, parent behavior, the gestation and breastfeeding period, nutritional status of early childhood in our patients with JIA, and to determine their relationship with disease activity, damage index, remission time, and relapse rate. Methods: In the present study were included data 170 JIA(55 boys and 115 girls)aged from 2 to 17 years,who received scheduled vaccination before the age of 2 years and before JIA onset against measles,parotitis,diphtheria and rubella.Incomplete vaccination means the reduced number of vaccine to age.In all patients the Ig G anti-vaccine antibodies levels were detected with ELISA.JIA categories were:oligoarthritis -73,polyarthritis -61,systemic-16 and enthesitisrelated arthritis-20.Data presented with median and 25%>75% Results: Incomplete vaccination against MMR was in 50 (42%)diphtheria in 85 (50%) of the JIA patients. doi = 10.1186/s12969-020-00470-5