Effect of antitumour necrosis factor treatment on circulating tumour necrosis factor levels and mortality after surgery in jaundiced mice

Abstract

Abstract Tumour necrosis factor (TNF) may play an important role in the increased incidence of complications after surgery in patients with obstructive jaundice. This study evaluated the effect of three different anti-TNF treatments, a monoclonal anti-TNF antibody (TN3), pentoxifylline and lactulose, on outcome after severe surgical trauma in mice with experimental biliary obstruction. Circulating serum TNF levels and mortality rate were monitored. Severe surgical trauma, such as renal ischaemia, in jaundiced mice resulted in increased levels of circulating TNF (3·5 ng/ml) and a high mortality rate (54 per cent). The three different anti-TNF treatments caused a significant reduction in postoperative levels of circulating TNF (TN3, P <0·001; pentoxifylline, P <0·01; lactulose, P <0·05). Treatment with TN3 and pentoxifylline did not lead to a significantly reduced mortality rate (36 and 44 per cent respectively). Only lactulose treatment produced a significantly reduced mortality rate (7 per cent, P <0·01). TNF is therefore not the only mediator responsible for death after surgery in jaundiced mice. Other mechanisms affected by lactulose are also involved.