Interleukin-1 family cytokines in liver cell death: a new therapeutic target for liver diseases

Introduction: Liver cell death represents a basic biological process regulating the progression of liver diseases via distinct mechanisms. Accumulating evidence has uncovered participation of interleukin (IL)-1 family cytokines in liver cell death. Upon activation of cell death induced by hepatotoxic stimuli, IL1 family cytokines released by hepatic dead cells stimulate recruitment of immune cells, which in turn influence inflammation and subsequent liver injury, thus highlighting their potential as therapeutic targets in liver diseases. Enhancing our comprehension of mechanisms underlying IL1 family cytokine signaling in cell death responses could pave the way for novel therapeutic interventions aimed at addressing liver cell death-related liver pathologies. Areas covered: This review summarizes the recent findings reported in preclinical and clinical studies on mechanisms of liver cell death, alongside participation of IL1 family members consisting of IL1α, ILβ, IL18, and IL33 in liver cell death and their significant implications in liver diseases. Expert opinion: Discovery of new and innovative therapeutic approaches for liver diseases will need close cooperation between fundamental and clinical scientists to better understand the multi-step processes behind IL1 family cytokines’ contributions to liver cell death.