Therapeutic efficacy of an antineutrophil monoclonal antibody, Urge-8, against acute necrotizing pancreatitis in rats

Background. Although they have critical roles in the defense mechanism against invading microorganisms, neutrophils may facilitate exacerbation of critical conditions associated with acute necrotizing pancreatitis by a discharge of granule contents into the organ tissues. Because of this constitution of neutrophils, the therapeutic efficacy of Urge-8, a mouse monoclonal antibody to neutrophils, on the survival of rats with experimentally induced acute necrotizing pancreatitis was investigated in vivo. Methods. Acute pancreatitis was induced by injection of trypsin mixed with sodium chenodeoxycholic acid into pancreatic ducts. Urge-8 was infused intravenously 30 minutes after pancreatitis was induced, a series of vital signs was taken, and plasma amylase level was estimated. Results. Hemorrhagic necrosis of the pancreas and intraabdominal bleeding were observed 1 hour after the pancreatitis-inducing drugs were injected, and death occurred at 240.9±24.6 minutes (mean±SD) in the control group. With Urge-8 administration, however, the survival time was significantly prolonged to 395.2±64.4 minutes (p=6.0×10 −10 versus control). Failure in the vital signs (mean arterial pressure, heart rate, and body temperature) was significantly ameliorated by injection of Urge-8. The plasma amylase level was elevated after pancreatitis was induced and peaked at 3 hours (4915±1966 IU/L in mean±SD). This level was suppressed during the first 3 hours by injection of Urge-8 (3372±1223 IU/L); however, the amylase level increased thereafter, becoming comparable with the peak in the control group, and then death occurred. Arterial blood gas and plasma electrolyte analyses showed that pH, base excess, and plasma potassium levels in the group treated with monoclonal antibody were significantly improved. Conclusions. It was suggested that neutrophils play some critical role in the exacerbation of acute necrotizing pancreatitis and its related symptoms. Although not capable of preventing death in our model, treatment with the antineutrophil monoclonal antibody Urge-8 after the onset of acute pancreatitis prolonged the survival time significantly.