Local and Systemic Zymogen Activation in Human Acute Pancreatitis

Background: Activation of trypsinogen and phospholipase A2 is an early event in pancreatic inflammation, but little is known about zymogen activation and the severity of human pancreatitis. Methods: Using a new fluoroimmunoassay we measured trypsinogen activation peptide (TAP) and phospholipase A2 activation peptide (PROP) in plasma and ascites in 25 patients with acute pancreatitis. TAP, PROP, Pro-PROP and pancreatic PLA2-I were measured in plasma for 14 days and in pancreatic necroses, ascitic fluid and pleural effusions. Results: All 16 patients with severe acute pancreatitis (SAP) had pancreatic necrosis, 10 developed systemic complications like sepsis, pulmonary or renal failure, 6 had infected necrosis, and 4 died. All 9 patients with mild pancreatitis (MAP) survived. Plasma TAP on admission was higher in patients with SAP than in those with MAP and increased in infected necroses. It did not correlate with systemic complications. Systemic PROP was not increased in complicated courses but was significantly higher in patients with MAP than in those with SAP on admission. Pro-PROP was higher in patients with SAP than in those with MAP but was not correlated with systemic complications. Plasma pancreatic PLA2-I was increased but not different in patients with SAP and those with MAP. In patients with pancreatic necrosis, TAP and PROP were highest, while in those with post-acute pancreatic abscess, only PROP and Pro-PROP were high. In patients with pleural effusion, TAP was low and PROP/ Pro-PROP were high. Conclusion: Trypsinogen and PLA2-I activation are early events in acute pancreatitis and the activation peptides can be detected in plasma. In the pancreas, trypsinogen activation is accompanied by PLA2-I activation in patients with pancreatic necrosis. However, in our study, organ complications in SAP patients was not associated with increased plasma PROP.

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