An overview of the biological and multifunctional roles of IL-38 in different infectious diseases and COVID-19.

Undoubtfully, the normal immune system can make a potential response to variable pathogens and neutralize or kill them depending on the type of infection through innate and acquired immunity. Cytokines have poly-peptide nature and are considered as signaling molecules that could amplify or alleviate immune responses besides their other biological functions. Interleukin 38 (IL-38) is a member of the IL-1 family cytokine that, however, its anti-inflammatory role has been observed in different autoimmune diseases like systemic lupus erythematosus (SLE), psoriasis, and Sjogren's syndrome; there is a controversy about the cytokine pro-inflammatory function. In the current review, we skimmed IL-38 structure, signaling mechanism, and its immunological functions, IL-38-producing immune cells. Also, we argued about the role of this cytokine in viral infections including hepatitis B (HBV), hepatitis C (HCV), influenza (Flu), and COVID-19. Also, it illustrated the IL-38 protective effects on sepsis. Moreover, we explained the modulatory role of IL-38 in the COVID-19 cytokine storm.