Proteases and protease inhibitors in cerulein-induced acute pancreatitis in rats

Background Proteases and protease inhibitors are important in acute pancrea titis (AP), although little is known about the time course in cerulein-indu ced AP in the rat. Materials and methods. AP was induced by supramaximal stimulation of cerule in, 10 mu g/kg/h, and during 72 h we measured lipase, amylase, albumin, pre kallikrein, factor X, alpha(1)-protease inhibitor, alpha(1)-macroglobulin, alpha(2)-antiplasmin, antithrombin ill tall in plasma) and macroscopic and histologic variables. Results. Within 12 h an edematous pancreatitis was evident with peak values of peritoneal exudate, pancreatic wet weight ratio, and plasma amylase and lipase activities. Histologically, edema and vacuolization were prominent already after 3 and 6 h, respectively, while inflammation, necrosis, and to tal histological score gradually increase to reach peak levels at 48 h. Pro enzymes and most plasma protease inhibitors decreased to low levels after 6 -12 h followed by a gradual increase. The sequential changes over time indi cate that kallikrein - kinin activation, and plasminogen activation are pro bably early events in cerulein-induced AP in rats, alpha(1)-Macroglobulin a nd (alpha(1-)protease inhibitor gradually decreased during the whole study period, probably being "second line" defense inhibitors. Levels above norma l were seen for alpha(2)-antiplasmin and factor X at 48 h, normalizing at 7 2 h. Conclusions. These results suggest that protease activation and protease in hibitor consumption occur in cerulein-induced AP in the rat. (C) 1999 Acade mic Press.