INDUCTION OF TUMOR-NECROSIS-FACTOR IN SEVERE ACUTE-PANCREATITIS AND ITS SUBSEQUENT REDUCTION AFTER HEPATIC PASSAGE

Background. Tumor necrosis factor (TNF) is rapidly gaining recognition as one of the early, critical mediators of several inflammatory condi tions, most notably endotoxic shock. The purposes of this study were t o determine whether TNF levels are raised in severe acute pancreatitis , thus pointing to its role as a potential mediator of the inflammator y process, and to determine the possible sites of production and uptak e. Methods. TNF levels were measured during a 2-hour period in a rat m odel of acute pancreatitis by using an antegrade infusion of artificia l bile. TNF levels were measured with a bioassay. Results. TNF levels increased proportionately with time and serum amylase level, reaching a mean value of 2700 pg/ml at 2 hours compared with sham operated rats (mean, 125 pg/ml) (p < 0.001). TNF levels in nonoperated controls wer e undetectable. These measurements were found to be independent of end otoxin production. In addition, selective sampling from the portal vei n, hepatic vein, and femoral artery showed hepatic degradation of TNF (p < 0.005), indicating that the liver may play an important role in p rotecting the host from multiple organ failure. Conclusions. Our resul ts showed that TNF levels are elevated in acute pancreatitis and may s uggest a role for this cytokine in the pathogenesis of the disease.