Cathepsin B inhibition in two models of acute pancreatitis.

The possible role of cathepsin B in the pathogenesis of two forms of acute pancreatitis was studied using the cathepsin B inhibitor known as E-64. In an edematous, nonfatal pancreatitis induced by supramaximal doses of cerulein, increases in the serum amylase and lipase levels were less pronounced in rats pretreated with E-64. Other parameters of pancreatic injury were unaffected by inhibition of cathepsin B. In a necrohemorrhagic type of pancreatic injury induced by retrograde infusion of bile salts into the pancreatic duct, E-64 partially attenuated increases in serum levels of amylase and lipase, and in addition, reduced the activation of trypsinogen. However, the high mortality in this model of pancreatitis was not modified.