Interleukins in liver disease treatment

Abstract

Cytokines play pleiotropic roles in human health and disease by regulating both innate and adaptive immune responses. Interleukins (ILs), a large group of cytokines, can be divided into seven families, including IL-1, IL-2, IL-6, IL-8, IL-10, IL-12, and IL-17 families. Here, we review the functions of ILs in the pathogenesis and resolution of liver diseases, such as liver inflammation (e.g., IL-35), alcohol-related liver disease (e.g., IL-11), non-alcoholic steatohepatitis (e.g., IL-22), liver fibrosis (e.g., Il-17a), and liver cancer (e.g., IL-8). Overall, IL-1 family members are implicated in liver inflammation induced by different etiologies, such as alcohol consumption, high-fat diet, and hepatitis viruses. IL-2 family members mainly regulate T lymphocyte and NK cell proliferation and activation, and the differentiation of T cells. IL-6 family cytokines play important roles in acute phase response in liver infection, liver regeneration, and metabolic regulation, as well as lymphocyte activation. IL-8, also known as CXCL8, is activated in chronic liver diseases, which is associated with the accumulation of neutrophils and macrophages. IL-10 family members contribute key roles to liver immune tolerance and immunosuppression in liver disease. IL-12 family cytokines influence T-cell differentiation and play an essential role in autoimmune liver disease. IL-17 subfamilies contribute to infection defense, liver inflammation, and Th17 cell differentiation. ILs interact with different type I and type II cytokine receptors to regulate intracellular signaling pathways that mediate their functions. However, most clinical studies are only performed to evaluate IL-mediated therapies on alcohol and hepatitis virus infection-induced hepatitis. More pre-clinical and clinical studies are required to evaluate IL-mediated monotherapy and synergistic therapies.

Keywords: Interleukins; Family members; Liver disease; Treatment; Clinical trials

Core Tip: Interleukins as a large group of cytokines play pleiotropic roles in liver homeostasis and disease by regulating both innate and adaptive immune responses. They can be divided into seven families, and all of them are involved in the pathogenesis and resolution of chronic liver diseases. Currently, interleukin-mediated therapies are applied in patients with hepatitis induced by alcohol or hepatitis virus infection.