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 proliferation during liver regeneration. It functions both as a comitogen and to induce the transcription factor nuclear factor-kappaB, which has antiapoptotic effects. On the other hand, TNF-alpha is the mediator of hepatotoxicity in many animal models, including those involving the toxins concanavalin A and lipopolysaccharide. TNF-alpha has also been implicated as an important pathogenic mediator in patients with alcoholic liver disease and viral hepatitis.