Tumor necrosis factor-α is a direct hepatocyte mitogen in the rat

We previously reported that tumor necrosis factor-α (TNF-α) increases in vivo hepatocyte mitoses and liver regeneration in rats. In the present studies, we used in vitro hepatocyte cultures to determine whether TNF-α itself was mitogenic or whether other cytokines (IL-1β and IL-6) that share similar actions with TNF-α might be involved. Hepatocytes were cultured with TNF-α (4, 40 or 400 U/ml), IL-1β (0.1, 1 and 10 ng/ml) or IL-6 (0.2, 2, or 20 ng/ml) for 24 h and 3 d. Incorporation of [³H]thymidine was increased significantly by TNF-α (40 and 400 U/ml) at 3 d. Both IL-1β and IL-6 at all concentrations significantly decreased [³H]thymidine incorporation at 3 d. These results indicate that TNF-α has a direct mitogenic action on hepatocytes. In contrast, IL-1β and IL-6 appear to suppress DNA synthesis in hepatocytes.