Hepatocyte growth factor protects mice against anti-Fas antibody-induced death

We have studied the efficacy of hepatocyte growth factor (HGF) in preventing anti-Fas antibody-induced hepatic apoptosis in mice and the resulting severe liver damage and death. HGF was intravenously administered at a dose of 500 mu g/kg to mice intraperitoneally injected with 6.7 or 10 mu g of anti-Fas monoclonal antibody, Jo2. Repeated administration of HGF dramatically prevented the death of mice induced by Jo2. HGF also diminished increases in both alanine transaminase and aspartate transaminase activity as well as total and direct bilirubin levels in line with histological findings of progressive improvement of the damaged liver. A single administration of HGF 1 h before Jo2 injection rescued the mice from death. A single administration of epidermal growth factor(ECF) mimicked HGF action in Jo2-injected mice, whereas neither growth hormone nor insulin-like growth factor-1 prevented death. These findings indicate that HGF or EGF effectively blocks death signalling pathways activated by the Fas and Fas ligand interaction. Med Sci Res 27:355-359 (C) 1999 Lippincott Williams & Wilkins.