ACUTE-PANCREATITIS INDUCED BY CYCLOSPORINE-A UNDER STIMULATION OF PANCREAS BY CERULEIN

Our purpose was to investigate enzymatically and morphologically the a cute effect of the immunosuppressive agent cyclosporin A (CsA) on the exocrine pancreas of rats. The intravenous injection of CsA 10 and 20 mg/kg body weight (BW) increased the content of pancreatic amylase and protein and decreased the content of pancreatic DNA. Histologically, we observed intra-acinar vacuolization and individual cell necrosis. U nder stimulation of the pancreas by two intraperitoneal injections of caerulein 5 mug/kg BW at 1-h intervals (which did not induce any evide nt change in the pancreas), CsA induced a significant increase in seru m amylase and in pancreatic wet weight in a dose-dependent manner. CsA at doses of 10 and 20 mg/kg BW produced a significant increase in the content of pancreatic amylase and protein. Macroscopically, we observ ed marked pancreatic edema, venous dilatation, and patchy hemorrhage. Histologically, there were significant differences in the severity of intra-acinar vacuolization, interstitial edema, neutrophil infiltratio n, individual cell necrosis, and hemorrhage, severity of which was dos e dependent. Pancreatic ductal erosion was particularly marked followi ng treatment with CsA 20 mg/kg BW. These findings indicate that CsA ac celerates abnormal pancreatic enzyme secretion and suggest that the th erapeutically recommended doses of CsA can induce acute pancreatitis u nder stimulation of the pancreas.