From bystander to key player: The mechanisms and therapeutic potential of IL-24 in liver diseases.

Interleukin-24 (IL-24) was initially identified during investigations on melanoma differentiation, and it is a pivotal member of the IL-10 family. As a secreted cytokine, IL-24 is recognized as a tumor suppressor cytokine that induces apoptosis and inhibits angiogenesis. The liver is a unique immunotolerant organ that maintains metabolic homeostasis while continuously responding to insults, such as viral infections, toxic substances, and metabolic stress. In recent years, accumulating evidence has elucidated the role of IL-24 in the initiation and progression of hepatocellular carcinoma (HCC), demonstrating that this cytokine may suppress tumor progression by inducing tumor cell death and modulating antitumor immunity. However, compared with its relatively well-characterized functions in HCC, the role of IL-24 in non-neoplastic hepatopathies remains less defined. Current evidence, primarily derived from in vivo and in vitro experiments, suggests that IL-24 may exert hepatoprotective effects against acute and chronic liver injury by alleviating endoplasmic reticulum stress. Additionally, IL-24 modulates hepatic stellate cell activation and influences proinflammatory cytokine release during liver fibrosis, whereas it affects hepatocyte autophagy and metabolic reprogramming in metabolic dysfunction-associated steatotic liver disease, thereby potentially mitigating disease progression. This review comprehensively delineates the molecular characteristics of IL-24 and summarizes research progress on its roles in non-neoplastic liver diseases, particularly focusing on the underlying molecular mechanisms and possible therapeutic implications. This study additionally highlights the limitations of current evidence and outlines future research directions, aiming to provide a basis for future investigation of IL-24-targeted intervention strategies.