The effects of a new human leukocyte elastase inhibitor (recombinant guamerin) on cerulein-induced pancreatitis in rats

Abstract

Background: Pancreatic and neutrophil elastase can aggravate or induce acute pancreatitis. Although increased elastase levels in the plasma of pancreatitis patients and animal models have been reported, the mechanism by which elastase is involved in the pathogenesis of acute pancreatitis has not yet been elucidated. We aimed to investigate the effects and the possible mechanism of a new human leukocyte elastase inhibitor (recombinant guamerin) in the treatment of cerulein-induced acute pancreatitis in rats. Methods: Fifty Sprague-Dawley rats were divided into three groups: a saline-infused control group (I), a cerulein-induced acute pancreatitis group (II), and a cerulein plus guamerin infusion group (III). Guamerin (1-2 mu mol/kg/h) was infused continuously in group III. The severity of pancreatitis was determined biochemically, histologically, and by cytokine changes between groups I, II and III. Results: Significant differences in serum amylase, lipase, and pancreatic wet weight were observed in each group, respectively (group 1; 2346.2 IU/L, 9.9 IU/L, 1.4 +/- 0.3 g, group II; 13,596.8 IU/L, 7439.4 IU/L, 2.2 +/- 0.5 g, group III; 9443.2 IU/L, 4516.3 IU/L, 1.7 +/- 0.6 g). Serum IL-6 and TNF-alpha [AU1]level peaked 1-4 h and 1-2 h. After the induction of pancreatitis, IL-6 and TNF-alpha levels were decreased in group III than group 11, (group 1; 13.1/ 4.0 pg/mL, group II; 198.5/63.2 pg/mL, group III; 102.1/13.1 pg/mL), but no significant difference in IL-1 beta was observed. Histologic gradings and severity, such as vacuolization, inflammation, lobular disarray, and edema of the pancreas, were significantly tower in the cerulein plus guamerin infusion group III. Conclusions: Recombinant guamerin, a new human leukocyte elastase inhibitor, may decrease the severity of pancreatitis and diminish pancreatic acinar cell injury by inhibition of neutrophilic infiltration and cytokine activation in the initial stage of cerulein-induced acute pancreatitis in rats.