Interleukin-19 deficiency exacerbates inflammation and fibrosis in ethanol/lipopolysaccharide-induced chronic pancreatitis.

Chronic pancreatitis (CP) is a progressive inflammatory disorder characterized by pancreatic fibrosis and loss of exocrine function. Interleukin-19 (IL-19) is an anti-inflammatory cytokine, but its role in the pathogenesis of CP remains unclear. This study aimed to investigate the protective function of IL-19 using an ethanol/lipopolysaccharide (LPS)-induced murine CP. CP was induced in wild-type (WT) and IL-19 knockout (KO) mice by administration of ethanol in drinking water combined with repeated intraperitoneal injections of LPS (3 mg/kg) for 10 weeks. Pancreatic injury, inflammation, and fibrosis were assessed histologically and molecularly. IL-19 KO mice developed markedly more severe pancreatitis than WT mice, as evidenced by elevated serum amylase levels, extensive fibrosis, acinar cell necrosis, loss of pancreatic architecture, and prominent inflammatory infiltration. In contrast, WT mice exhibited only mild pancreatic injury with largely preserved acinar structure. mRNA expression levels of tumor necrosis factor-α and transforming growth factor-β in the pancreas were significantly higher in IL-19 KO mice, consistent with enhanced inflammatory and fibrotic responses. Notably, pancreatic IL-19 mRNA expression was significantly upregulated in CP, suggesting an endogenous compensatory mechanism. IL-19 deficiency worsens ethanol/LPS-induced chronic pancreatitis, indicating that endogenous IL-19 protects against inflammation and fibrosis and may serve as a therapeutic target.