The protective effect of cyclosporin A on experimentally-induced acute hepatic injury in mice.

Abstract

When heat-killed Propionibacterium acnes (P. acnes) and a small amount of endotoxin lipopolysaccharide (LPS) were intravenously injected into mice at a week's interval, most of them died of massive hepatic cell necrosis. This experimentally-induced acute liver injury was significantly inhibited by cyclosporin A (CsA), resulting in a remarkable improvement of the survival rate. This protective effect of CsA on acute liver injury was also histopathologically confirmed. To study the mechanism by which CsA protected the mice from fatal hepatic injury, adherent cells prepared from the murine liver 7 days after P. acnes injection were incubated with LPS in the presence of CsA, and the effect of CsA on the production of the cytotoxic factor from the adherent cells was estimated. As a result, CsA inhibited the activation of liver adherent cells and suppressed the release of the cytotoxic factor.