IL-33/ST2 axis emerges as diagnostic biomarker and therapeutic target across diverse liver diseases

Liver diseases, encompassing conditions like hepatitis B virus (HBV) infection, steatohepatitis, fibrosis, and hepatocellular carcinoma, represent a significant global health burden. Current diagnostic and therapeutic strategies often face limitations in early detection and effective intervention. The interleukin-1 (IL-1) family of cytokines, particularly IL-33, has gained attention for its role in inflammation and tissue damage. Understanding the specific mechanisms and diagnostic potential of IL-33 in liver pathologies could pave the way for novel clinical approaches.

This narrative review systematically summarized existing literature on IL-33 expression characteristics, mechanisms, and targeted strategies across various liver pathologies. The authors synthesized findings from studies investigating IL-33 in conditions like hepatitis B virus (HBV) infection, acute or chronic toxic liver injury, steatohepatitis, fibrosis, cirrhosis, hepatic ischemia/reperfusion injury, and hepatocellular carcinoma. The methodology involved a comprehensive literature search to identify relevant research on the IL-33/ST2 axis in liver disease contexts, aiming to consolidate recent progress and identify future directions.

The review highlighted that IL-33 is abundantly present in the nucleus of epithelial cells from barrier tissues, blood vessels, and fibroblast-like cells under physiological conditions. Upon pathological stimuli such as cell damage or tissue injury, IL-33 is released from these cells and binds to the ST2 receptor, a member of the toll-like receptor (TLR)/IL-1 receptor superfamily, initiating inflammatory responses. The IL-33/ST2 axis was consistently implicated in regulating multiple inflammatory diseases, tissue damage, and fibrosis within the liver. Specifically, its aberrant expression was identified across a spectrum of liver pathologies, including HBV infection, various forms of liver injury, steatohepatitis, and hepatocellular carcinoma. This axis plays a crucial role in the development and progression of liver pathologies by modulating immune responses and tissue remodeling processes. The synthesis of evidence strongly suggests that the dysregulated IL-33/ST2 axis acts as a pivotal mediator, making it a promising candidate for both diagnostic biomarker development and targeted therapeutic intervention in diverse liver diseases.