Background: Proteases play an important role in the pathogenesis of acute pancreatitis (AP). Systemic release of proinflammatory cytokines such as tumor necrosis factor (TNF) and interleukin-6 (IL-6) has been demonstrated in AP, yet the mechanism of activation remains unclear. Previous studies in our laboratory demonstrated the influence of pancreatic enzymatic content on the outcome of AP. Reduction of pancreatic enzyme content reduces the severity of pulmonary lesions and hepatic damage and the mortality in AP in rats. However is not known whether the amount of pancreatic enzymes influences the production of proinflammatory cytokines. The present study assesses the effect of acute reduction of pancreatic enzymatic content on the early cytokine response in the experimental AP.
Methods: Rats were divided in two groups: Group I (submitted to reduction of pancreatic enzymes by intravenous administration of physiological doses of caerulein: 0.13m Kg/h for three hours) and Group II (without reduction of pancreatic enzymatic content). AP was induced in rats of both groups by infusion of 5% sodium taurocholate into the pancreatic duct. Two hours after the induction of AP,TNF, IL-6 and TAP(trypsinogen activation peptide) were determined in serum and ascitis.
Results: Animals with reduction of pancreatic enzyme content showed a significant decrease of proinflammatory cytokins (TNF in ascitis and IL-6 in serum) as well as a reduction of TAP levels in plasma and ascites (Table 1).
Conclusion: Reduction of pancreatic enzyme content disminishes the production of proinflammatory cytokines, suggesting that the enzimatic content of the pancreas plays an important role in the pathogenesis of experimental AP.
TNF(ascitis) pg/ml IL-6 (serum) pg/ml TAP (plasma)nmol/L TAP (ascitis) nmol/L
reduction (n=7) 217 ± 99 * 54 ± 32 * 1.0 ± 0.2 * 23 ± 6 *
reduction (n=7) 603 ± 68 469 ± 192 3.6 ± 0.7 72 ± 11
* p < 0.05