Tumor necrosis factor-alpha increases hepatic DNA and RNA and hepatocyte mitosis

Tumor necrosis factor-alpha (TNF) has been reported to increase DNA synthesis in normal rat liver. Therefore, we examined the effects of TNF on rat liver regeneration. TNF, 1.5 micrograms ip every 4 h for 5 d, significantly increased hepatic DNA and RNA contents of regenerating and sham operated livers by up to 45%. Mitotic figures in sham operated liver, usually rare, were increased substantially by TNF. ODC mRNA content and enzyme activity were increased in regenerating liver, and were further increased by TNF. These data indicate that TNF, although not specific for regenerating liver, is a potent stimulus for hepatocyte DNA synthesis and mitosis.