Acute pancreatitis induced by cyclosporin a under stimulation of pancreas by caerulein

Our purpose was to investigate enzymatically and morphologically the acute 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. Under stimulation of the pancreas by two intraperitoneal injections of caerulein 5 µg/kg BW at 1-h intervals (which did not induce any evident change in the pancreas), CsA induced a significant increase in serum amylase and in pancreatic wet weight in a dose-dependent manner. CsA at doses of 10 and 20 mg/kg BW produced a significant in-crease in the content of pancreatic amylase and protein. Macroscopically, we observed marked pancreatic edema, venous dilatation, and patchy hemorrhage. Histologically, there were significant differences in the severity of intra-acinar vacuolization, interstitial edema, neutrophil infiltration, individual cell necrosis, and hemorrhage, severity of which was dose dependent. Pancreatic ductal erosion was particularly marked following treatment with CsA 20 mg/kg BW. These findings indicate that CsA accelerates abnormal pancreatic enzyme secretion and suggest that the therapeutically recommended doses of CsA can induce acute pancreatitis under stimulation of the pancreas.