MECHANISMS OF HEPATIC TOXICITY-I - TNF-INDUCED LIVER-INJURY

Tumor necrosis factor-alpha (TNF-alpha) functions as a two-edged sword in the liver. TNF-alpha is required for normal hepatocyte proliferati on during liver regeneration. It functions both as a comitogen and to induce the transcription factor nuclear factor-kappa B, which has anti apoptotic effects. On the other hand, TNF-alpha is the mediator of hep atotoxicity in many animal models, including those involving the toxin s concanavalin A and lipopolysaccharide. TNF-alpha has also been impli cated as an important pathogenic mediator in patients with alcoholic l iver disease and viral hepatitis.