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Background/aim: In acute pancreatitis, it is believed that generalized activation of pancreatic zymogens leads to autodigestion of the pancreas and if excessive to systemic organ injury. Under physiological circumstances, secretory phospholipase A(2) type I (sPLA(2)-I) is activated by trypsinogen, but the extent of this activation in acute pancreatitis is unclear. The aim of this study was to assess time course and level of activation of sPLA(2)-I and trypsinogen in acute pancreatitis, relative to severity., Methods: 246 patients were enrolled into a prospective European multicenter study. 137 patients had mild and 35 had severe acute pancreatitis, and there were 74 control patients. Urinary samples were taken on admission and at 6-hour intervals for 48 h, then every 12 h up to 72 h, and finally daily for at least 5 days for measurement of the activation peptide of sPLA(2)-I (pro-phosphatase A(2); PROP) and trypsinogen activation peptide., Results: The median maximum PROP values were significantly elevated 48 h after symptom onset in patients with severe acute pancreatitis [1.52 (95% CI 0.8-2.9) nmol/l] as compared with patients with mild acute pancreatitis [0.72 (0.55-1) nmol/l, p = 0.002] and controls [0.49 (0.22-1.2) nmol/l, p = 0.001], but not before or after this time point. The best cutoff point for urinary PROP to predict overall severity was >1 nmol/l < or =48 h after symptom onset (negative predictive value = 88%), but the PROP levels failed to predict the development of multi-organ dysfunction., Conclusions: Activation of sPLA(2)-I is associated with the early pathogenesis of acute pancreatitis, but not in the development of distant organ damage. This observation raises questions as to the theory of generalized zymogen activation being a principle mechanism involved in the pathogenesis of distant organ damage in acute pancreatitis., (Copyright 2002 S. Karger AG, Basel and IAP)

Neutrophil sequestration and activation in the pulmonary vasculature and interstitium are important in acute lung injury. Phospholipase A2 plays an important part in the production of potent inflammatory mediators in this syndrome. We used our ELISA for type 1 prophospholipase A2 activation peptides, which have the aminoacid sequence Asp-Ser-Gly-Ile-Ser-Pro-Arg (DSGISPR), to show that DSGISPR concentrations in plasma and urine are a sensitive and specific marker of acute lung injury in patients admitted to intensive care. The detection of DSGISPR in the plasma of 11 of 50 unselected patients had a sensitivity of 100% and a specificity of 93% for the presence or future development of acute lung injury.