Effect of TNF gene depletion on liver regeneration after partial hepatectomy in mice

Background. Tumor necrosis factor-alpha (TNF) is thought to art as a stimut lator for initiating hepalocyte proliferation after partial hepatetectomy ( PH). At the same time TNF induces a series of inflammatory responses that m ay Be detrimental for the liver and other remote organs. The purpose of thi s study runs to investigate the effect of TNF on the pathophysiologic state after PH. Methods. Wild-type (TNF+/+) and TNF-deficient (TNF-/-) mice underwent 70% P H. Hepatocyte proliferation was assessed by bromodeoxyuridine labeling and mitotic index. Liver function was evaluated by alanine aminotransferase (AL T) and total bilirubin levels in serum after PH. Myeloperoxidase activity i n the liver and lung was measured as a marker for neutrophil activation. Results. No differences were observed in liver regeneration or hepatocyle p roliferation between TNF+/+ and TNF-/- mice The survival of TNF-/- mice on day I after PH was significantly higher than that of TNF+/+ mice, but both groups had similar survival thereafter The ALT level was significantly high er in TNF+/+ mice 6 hours after PH and myeloiproxidase activities in both l iver and lung were markedly elevated in TNF+/+ mice compared with TNF-/- mi ce. Conclusions. These findings demonstrate that TNF gene-depleted mice do not demonstrate delayed liver regeneration but no suppress neutrophil activatio n after PH compared with results in wild-type (TNF+/+) mice.