Induction of tumor necrosis factor in severe acute pancreatitis and its subsequent reduction after hepatic passage

Abstract

Background: Tumor necrosis factor (TNF) is rapidly gaining recognition as one of the early, critical mediators of several inflammatory conditions, most notably endotoxic shock. The purposes of this study were to determine whether TNF levels are raised in severe acute pancreatitis, thus pointing to its role as a potential mediator of the inflammatory process, and to determine the possible sites of production and uptake.

Methods: TNF levels were measured during a 2-hour period in a rat model of acute pancreatitis by using an antegrade infusion of artificial 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 were undetectable. These measurements were found to be independent of endotoxin production. In addition, selective sampling from the portal vein, hepatic vein, and femoral artery showed hepatic degradation of TNF (p < 0.005), indicating that the liver may play an important role in protecting the host from multiple organ failure.

Conclusions: Our results showed that TNF levels are elevated in acute pancreatitis and may suggest a role for this cytokine in the pathogenesis of the disease.