Interleukin 10 reduces the severity of acute pancreatitis in rats

Background & Aims: Previous studies have documented the effectiveness of interleukin (IL)-10 if given before the onset of experimental acute pancreatitis. This study examined whether IL-10, a cytokine that inhibits macrophage release of inflammatory mediators, would alter the severity of acute pancreatitis if given before or after the induction of disease. Methods: Eighty-four Sprague-Dawley rats were divided into four groups. Group 1 received intravenous saline, and groups 2, 3, and 4 received intravenous cerulein (8.5 mu g . kg(-1). h(-1)). Group 3 was also given 150,000 U of intraperitoneal IL-10 1 hour before cerulein infusion and every 3 hours thereafter. Group 4 received 150,000 U intraperitoneal IL-10 2 hours after cerulein infusion and every 3 hours thereafter. Serum amylase and tumor necrosis factor (TNF)-alpha levels were measured before and 3, 9, or 15 hours after induction of pancreatitis. Animals were killed at these time points. Pancreata were analyzed for edema and TNF-alpha mRNA and TNF-alpha protein concentrations and were graded histologically. Results: Serum amylase, TNF-alpha mRNA, and TNF-alpha protein levels, pancreatic edema, and histological score were significantly reduced when IL-10 was administered either before or after induction of pancreatitis. Serum TNF-alpha levels were undetectable. Conclusions: IL-10 attenuated the severity of experimental acute pancreatitis if given either before or after the induction of the disease. These results are consistent with the hypothesis that the macrophage is important in determining the severity of acute pancreatitis in this model.