TNF-α 及IL-1 分別在Concanavalin A 及酒精誘導的急性肝炎所扮演之角色

Abstract

Autoimmune hepatitis is a chronic inflammation in the liver that occurs when the body‘s immune system attacks the liver. Although the cause of autoimmune hepatitis is not entirely clear, some diseases, toxins and drugs may trigger autoimmune hepatitis insusceptible people, especially in women. Concanavalin A (Con A)-induced hepatitis in mice is thought to mimic autoimmune hepatitis in human. In this study, we investigated the role of TNF-α and IL-1 in Con A-induced hepatitis. We found that Con A-triggered serum ALT and AST production and neutrophil infiltration in liver were markedly reduced in TNF-α-/- mice, TNFR1-/- mice and IL-1R-/- mice. Furthermore, the number of CD4+ T cells in liver was also reduced in mice deficient of TNF-α, and TNFR1. Overall our findings imply that both TNF-α and IL-1 play important roles in mediating Con A-induced hepatitis by regulating the recruitment of neutrophils into liver. Although the histopathology of early alcoholic liver disease, i.e., steatosis,inflammation, and necrosis, has been well documented, the exact mechanisms of pathogenesis of this devastating disease are still unknown. In this study, we established the model of acute-alcohol hepatitis to investigate the role of TNF-α in ethanol-induced acute liver injury. We found that serum ALT levels in TNFR1-deficient mice were markedly reduced in alcohol-induced liver Injury. Neutrophil infiltration in alcohol-induced liver injury was also reduced in TNFR1-deficient mice. These results demonstrated that TNF-α was involved in alcohol-induced hepatitis by mediating the recruitment of neutrophils into liver.