LAUSR

Abstract Lipopolysaccharide/d‐Galactosamine (LPS/d‐Gal)‐induced acute liver injury is characterized by significant inflammatory responses including TNF‐&agr; and interleukin‐6 (IL‐6) and is a widely applied experimental model for inflammation research. TNF‐&agr; is critical in the progression of LPS/d‐Gal‐induced liver injury. However, the role of IL‐6 in this model is still unknown. In the present study, we aim to elucidate the involvement of IL‐6 in the pathogenesis of acute liver injury induced by LPS/d‐Gal in mice and its underlying mechanism. To induce acute liver injury, LPS (50 &mgr;g/kg body weight) and d‐Gal (400 mg/kg body weight) were injected intraperitoneally in the C57BL/6 mice. The vehicle (saline) or a single dose of recombinant IL‐6 (200 &mgr;g/kg body weight) was administered 2 h prior to LPS/d‐Gal injection. Mice were sacrificed 2 h and 6 h after LPS/d‐Gal injection. The results indicated that IL‐6 treatment could protect mice from LPS/d‐Gal‐induced tissue damage, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) elevation, as well as hepatocyte apoptosis and inflammation. Furthermore, in vitro study showed that IL‐6 treatment could significantly suppress LPS‐triggered expression of proinflammatory cytokines and chemokines, TNF‐&agr;, RANTES and MCP‐1 in macrophages while promoting the expression of M2 markers, such as Arg‐1 and Mrc‐1 in macrophages. Taken together, these findings revealed a novel and unexpected role of IL‐6 in ameliorating LPS/d‐Gal‐induced acute liver injury via regulating inflammatory responses in hepatic macrophages. HighlightsIL‐6 attenuated LPS/d‐Gal‐induced acute liver injury.IL‐6 alleviated hepatocytes apoptosis in LPS/d‐Gal‐induced acute liver injury mice.IL‐6 inhibited LPS/d‐Gal‐induced production of inflammatory cytokines.IL‐6 suppressed macrophages M1 activation and promoted macrophages M2 activation.