EFFECTS OF C1-ESTERASE INHIBITOR IN 3 MODELS OF ACUTE-PANCREATITIS

The present studies were done to evaluate the therapeutic potential of C1-esterase inhibitor in three different models of acute pancreatitis : (1) Edematous pancreatitis with acinar cell necrosis was induced by 7-h ip injections of 50 mu g/kg cerulein in mice; (2) Hemorrhagic panc reatitis was induced by feeding a choline-deficient, ethionine-supplem ented (CDE) diet in mice; and (3) Hemorrhagic pancreatitis was induced by retrograde infusion of 0.6 mL 5% sodium-taurocholate Into the panc reatic duct in rats. C1-esterase inhibitor was given at 100 mg/kg iv b efore the onset of pancreatitis and at certain intervals thereafter. T he severity of pancreatitis was assessed at various times after its on set by determination of serum amylase, by grading of histological alte rations, and by determination of survival (survival determined only in models of hemorrhagic pancreatitis). In some of the models, C1-estera se inhibitor slightly ameliorated the degree of histological alteratio ns; the increase in serum amylase was reduced by C1-esterase inhibitor only in CDE diet-induced pancreatitis. In all three models, C1-estera se inhibitor, however, failed to cause major beneficial effects and al so failed to improve survival in taurocholate and diet-induced pancrea titis. Additional studies in 12 patients with acute pancreatitis showe d that C1-esterase inhibitor activity was markedly increased in serum of all patients during the first 8 d of the disease, suggesting that C 1-esterase inhibitor behaves like an acute phase protein. Taken togeth er the results from the animal and the human studies, C1-esterase inhi bitor appears to only have a limited potential for treatment of acute pancreatitis.