ANTI-TNF-ALPHA THERAPY IMPROVES SURVIVAL AND AMELIORATES THE PATHOPHYSIOLOGIC SEQUELAE IN ACUTE-PANCREATITIS IN THE RAT

BACKGROUND: Elevated levels of tumor necrosis factor-alpha (TNF alpha) have been measured in a lethal model of acute pancreatitis (AP) and m ay contribute to the pathophysiologic sequelae of the disease. METHODS : TO determine the significance of anti-TNF alpha 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 wi th anti-TNF alpha antibody 15 minutes prior to induction of AP (n = 30 ). Five treated and 5 untreated rats were killed at various time perio ds up to 72 hours to provide temporal characterization of TNF alpha ac tivity in AP. RESULTS: A burst Of TNF alpha activity in the serum of u ntreated pancreatitis animals between 1 and 3 hours after induction of the disease is prevented by pretreatment with anti-TNF alpha antibody , CONCLUSIONS: These findings provide a plausible mechanism for the im provement in biochemical and histologic parameters as well as in overa ll survival in an experimental model of acute pancreatitis in the rat.