Possible role of tumor necrosis factor-α for induction of hepatic cell necrosis

Abstract

In mice, peritoneal injection of tumor necrosis factor-α (TNF-α) alone did not cause the liver injury, but simultaneous injection of TNF-α and D-galactosamine (GalN) induced severe hemorrhagic liver cell necrosis which was protected by nifedipine, verapamil, dantrolene, calmidazolium and indomethacin. In cultured rat hepatocytes, neither TNF-α alone nor simultaneous addition of TNF-α and GalN induced liver cell injury. But the serum of a rat intravenously administered with TNF-α caused the cell injury which was protected by nifedipine, verapamil, TMB-8, calmidazolium, indomethacin and aprotinin.
These results suggest that TNF-α is not the factor which can cause liver cell injury by itself, but it may induce some new factors related to liver cell injury involving intracellular Ca²⁺, protease, prostaglandin and complement.