Anti-TNFα therapy improves survival and ameliorates the pathophysiologic sequelae in acute pancreatitis in the rat

BACKGROUND: Elevated levels of tumor necrosis factor-alpha (TNFα) have been measured in a lethal model of acute pancreatitis (AP) and may contribute to the pathophysiologic sequelae of the disease. METHODS: To determine the significance of anti-TNFα therapy on survival and disease manifestations in a clinically relevant model of AP, a rat model was developed using a retrograde pancreatic ductal infusion of bile. Animals were randomized to no treatment (n = 30) or treatment with anti-TNFα antibody 15 minutes prior to induction of AP (n = 30). Five treated and 5 untreated rats were killed at various time periods up to 72 hours to provide temporal characterization of TNFα activity in AP. RESULTS: A burst of TNFα activity in the serum of untreated pancreatitis animals between 1 and 3 hours after induction of the disease is prevented by pretreatment with anti-TNFα antibody. CONCLUSIONS: These findings provide a plausible mechanism for the improvement in biochemical and histologic parameters as well as in overall survival in an experimental model of acute pancreatitis in the rat.