Synergistic effects of antibodies against high-mobility group box 1 and tumor necrosis factor-α antibodies ond-(+)-galactosamine hydrochloride/lipopolysaccharide-induced acute liver failure

High‐mobility group box 1 ( HMGB 1) protein is released into the serum after tissue damage, and serves as a warning signal to enhance the inflammatory response. Acute liver injury is one of the diseases that starts with tissue damage and ends with systemic inflammation. We used d ‐(+)‐galactosamine hydrochloride ( d ‐ G al N )/lipopolysaccharide ( LPS )‐treated mice as an acute liver injury model to explore the functions of HMGB 1 in more detail. HMGB 1 is released into the serum at a very early stage of d ‐ G al N / LPS ‐induced acute liver injury. It upregulates the expression of tumor necrosis factor‐α ( TNF ‐α), interleukin‐6, inducible nitric oxide synthase, and tissue factor. TNF ‐α and HMGB 1 form a positive feedback loop to amplify the downstream signals. mAbs against HMGB 1 and TNF ‐α have synergistic effects in protecting mice from d ‐ G al N / LPS ‐induced acute liver failure. The results suggest that HMGB 1 is a key mediator in d ‐ G al N / LPS ‐induced acute liver injury. Tissue damage and cell necrosis shortly after administration of d ‐ G al N and LPS lead to early HMGB 1 release, and HMGB 1 acts synergistically with TNF ‐α to promote pathological processes in acute liver failure.