Selective inhibition of cyclooxygenase-2 (COX-2) reduces prostaglandin E2 production and attenuates systemic disease sequelae in experimental pancreatitis.

Background/Aims: Prostaglandins and prostaglandin-derived mediators play an important role in mediating the systemic inflammatory response in acute pancreatitis. COX (cycloozygenase) is the key enzyme of prostaglandin synthesis. Whereas COX-1 produces prostaglandin mediators for physiological reactions, COX-2 is overexpressed in acute pancreatitis. The aim of this study was to investigate whether a selective COX-2 inhibitor alters prostaglandin production and attenuates systemic disease sequelae in severe acute pancreatitis in rats. Methodology: Severe acute pancreatitis was induced in 36 rats by standardized intraductal infusion of bile salt and intravenous cerulein infusion. Six hours after acute pancreatitis induction, rats were randomized to receive either no COX inhibition (saline), nonselective COX inhibition by indomethacin (3mg/kg, i.v.) or selective COX-2 inhibition by NS-398 (10mg/kg, i.v.). Serum concentrations of prostaglandin E2 were measured before and after acute pancreatitis induction and 24 hre aller starting therapy. Routine cardiorespiratory and renal parameters were monitored to asses ergan function. Results: Animals treated with the selective COX-2 inhibitor had significantly lower prostaglandin E2 values (211±17 vs. 366±37 and 435 ± 13pg/mL), produced more urine (18±4 vs. 13±3 and 12±3mL/6-24h) and had sigmficantly fewer episodes of respirstory distress (defined vs. a pO 2 50mmHg for >15 min; 12 vs. 57 and 71%) during the observation period than animals without or with nonselective COX inhibition. Conclusions: Selective inhibition of COX-2 reduces prostaglandin E2 serum levels in this model of acute pancreatitis. This together with improved renal and respiratory function suggesis an attenustion of the systemic response to pancreatic injury. COX-2 inhibition may be another step toward optimizing therapy in severe acute pancreatitis.