Department of Pathology, Yale University School of Medicine, New Haven, Connecticut.
Chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infection affect >500 million people worldwide and are significant causes of liver cirrhosis and hepatocellular carcinoma. The pathogenesis of HBV and HCV infection can vary widely with respect to the outcome of initial infection to self-resolving acute or chronic disease, the extent of viremia and liver inflammation during chronic infection, and the eventual development of liver cirrhosis and hepatocellular carcinoma. The host immune response is an important factor in the variable consequences of these infections, because the innate and adaptive intrahepatic antiviral responses are an intricate balance of immune effector cells and cytokines that control virus replication but can also cause liver damage. IL-22 is an important cytokine that plays a pleiotropic protective, but sometimes also pathological, role in several tissues/organs, including the liver. Therefore, IL-22 is likely to be an important factor in the pathogenesis and clinical outcome of HBV and HCV infection. However, the precise beneficial, and possible detrimental, effects of this cytokine may vary among different disease states that are associated with distinct inflammatory microenvironments. This review summarizes our understanding of the protective and pathological activities of IL-22, with an emphasis on the liver, and discusses the implications of these effects as they relate to viral hepatitis.