The significance of IL-19 in the liver: crosstalk among inflammation, metabolism, and fibrosis

Interleukin (IL)-19, a member of the IL-10 cytokine family, has been recognized for its anti-inflammatory functions in conditions such as inflammatory bowel disease and dermatitis. However, its role in liver diseases remains largely unexplored. In this study, we investigated the pathophysiological significance of IL-19 using a murine model of nonalcoholic fatty liver disease (NAFLD/NASH). Mice lacking IL-19 fed a customized CDAHFD diet exhibited delayed weight recovery, exacerbated inflammatory cell infiltration, enhanced fibrosis, and elevated serum liver injury markers and pro-inflammatory cytokines compared with wild-type mice. IL-19 was primarily produced by Kupffer cells in the liver and acted on hepatocytes to activate STAT3 signaling, suppress lipogenic gene expression, and enhance ATP production and PPARα activity. These actions shifted fatty acid utilization toward energy metabolism, thereby attenuating lipid accumulation and hepatocellular injury. Collectively, our findings suggest that IL-19 functions as a protective regulator suppressing steatosis and fibrogenesis. Future studies integrating steatosis and fibrosis models are warranted to further delineate its mechanisms and to evaluate the potential of IL-19 as a biomarker and therapeutic target in chronic liver diseases.