key: cord-0930367-li19j87q authors: Roohi, Azam; Soroosh, Pejman title: May Interferon λ be a novel therapeutic approach against COVID-19? date: 2020-10-22 journal: Med Hypotheses DOI: 10.1016/j.mehy.2020.110351 sha: 9a346478ac93af6e93f3eb52360b65985753218e doc_id: 930367 cord_uid: li19j87q nan Azam Interferons are a family of cytokines best known for their anti-viral effects. They play a critical role in slowing down of viral multiplication. These cytokines are subdivided into three types. The type I IFNs (IFN-α/β) possess 13 members including IFN-α/β. The type II IFN has just one member, IFN-γ. The type III IFNs (IFN-λ) are made up of 4 members namely IFN-λ1 to IFN-λ4. According to the recent investigations all three types of interferons can either activate or regulate immune response [3, 4] . Although type I and type III IFNs have even more immune activities in common, their functions are not fully redundant and IFN-λs have specific characteristics which may make them an appropriate therapy against COVID-19: 1-While the expression of type I IFNs receptors are ubiquitous, the expression of IFN-λ receptors are limited to the tissues with relatively high numbers of epithelial cells such as lung, skin, gastrointestinal and respiratory tracts. This dual pattern of receptors distribution gives a unique potential to the IFN-λ family for tailored targeting special tissues [5] . 2-The yin-yang concept is seen in each medicinal component. Application of both type I and type III IFNs is followed by a range of side effects [6] . Nonetheless, due to the restricted expression of the IFN-λ family receptors, fewer side effects would be expected. In addition, the type I IFNs have a central role in lung inflammatory response [7] . 3-At mucosal surfaces IFN-λ family plays a significant role in driving anti-viral immune response [8] . 4-During a mouse Influenza A infection, IFN-λ and not IFN-α was chiefly produced by intranasal epithelial cells [9] . 5 -In a mouse model, both IFN-λ and IFN-α could prevent Influenza virus replication, however, only IFN-λ could hinder spreading of the virus to the lung [10] . Previously, low-dose IFN-α prophylaxis could reduce the severity of acute respiratory illness during an influenza pandemic [11] . It seems IFN-λ therapy could be advantageous during COVID-19 pandemic if it is locally administrated directly to mucosal barriers where the earliest anti-viral defense occurs with less inflammatory side effects. [12] . Race to find COVID-19 treatments accelerates The Dual Nature of Type I and Type II Interferons Type I interferons in infectious disease IFN-lambda (IFN-lambda) is expressed in a tissue-dependent fashion and primarily acts on epithelial cells in vivo Impact of Type I and III Interferons on Respiratory Superinfections Due to Multidrug-Resistant Pathogens Type I Interferons as Regulators of Lung Inflammation. Front Immunol Interferon-lambda orchestrates innate and adaptive mucosal immune responses Low-dose oral interferon alpha as prophylaxis against viral respiratory illness: a double-blind, parallel controlled trial during an influenza pandemic year. Influenza Other Respir Viruses IFN-lambda prevents influenza virus spread from the upper airways to the lungs and limits virus transmission. Elife Lambda interferon is the predominant interferon induced by influenza A virus infection in vivo Shared and Distinct Functions of Type I and Type III Interferons The authors declare they have no conflict of interest. The authors declare that they have no conflict of interest.