The role of pituitary-adrenal counterregulation of inflammation in cerulein-induced pancreatitis: A comparison between Fischer and Lewis rats

The role of the hypothalamio-pituitary-adrenal axis (HPA axis) in acute pancreatitis has not yet been clarified. In the present study, the concentrations of serum corticosterone and amylase, the severity of pancreatic edema, and the histology of the pancreas during cerulein-induced pancreatitis were compared in two strains of rats whose HPA axes have been reported to be hyperresponsive (Fischer female) and hyporesponsive (Lewis female) to inflammatory mediators. First, we confirmed that the secretory response of corticosterone to lipopolysaccharide was remarkably blunted in Lewis rats compared with Fischer rats. With a single intraperitoneal injection of cerulein at a dose of 50 mu g/kg, the serum corticosterone of Fischer rats increased promptly, and their serum levels were significantly higher than those of Lewis rats at all points after the induction of pancreatitis. The edema formation and infiltration of inflammatory cells into the pancreas were more severe in Lewis rats than in Fischer rats. The serum amylase concentration was not significantly different between the two strains, except at 2 h after the induction of pancreatitis. The in vitro study using dispersed pancreatic acini showed that there was no significant difference in cerulein-stimulated amylase secretion between the two strains. These findings suggest that the responsiveness of the HPA axis and the consequent secretion of glucocorticoids might modify the pathological features of acute pancreatitis.