The Protective Effect of Cyclosporine A on Anti-Fas Antibody-Induced Hepatitis in Mice

The effect of cyclosporine A (CsA) on anti-Fas antibody-induced hepatitis was studied. The administration of anti-Fas antibody (250 microg/kg) to mice elevated plasma alanine aminotransferase (ALT) activity at 3 hr. This anti-Fas antibody-induced elevation of ALT was inhibited by treatment with CsA (10, 30 and 100 mg/kg) in a dose-dependent manner. Anti-Fas antibody administration elevated CPP32-like protease activity at 3 hr in mouse liver, and this elevation of CPP32-like activity was inhibited by treatment with CsA. The present results show that CsA treatment inhibits the anti-Fas antibody-induced apoptotic process of hepatitis, at least in part, by affecting a reaction upstream of CPP32-like protease activation.