Selektive Cyclooxygenase-2 Inhibition vermindert systemische Reaktionen bei akuter Pankreatitis

Abstract

Prostaglandins (PG) and PG-derived mediators play an important role in mediating the systemic inflammatory response in acute pancreatitis (AP). Whereas COX-1 produces PG mediators for physiological reactions, COX-2 is overexpressed in AP. The present study investigates whether a selective COX-2 inhibitor alters PG production and attenuates systemic disease sequelae in severe AP in the rat. Six hours after induction of severe AP by intraductal bile salt infusion and i.v. cerulein, 36 rats were randomized for therapy with: [A] the selective COX-2 inhibitor NS-398 (10 mg/kg), [B] indomethacin (3 mg/kg) for non-selective COX inhibition, or [C] saline. Prostaglandin E2 (PGE-2) was measured using ELISA before and after AP induction and 24 h thereafter. Assessment of organ function included measurements of heart rate, blood pressure, blood gases and urine output at 0,6 and 24 h. At 24 h following AP induction, NS-398-treated animals had significantly lower serum levels of PGE-2 (211±17 pg/ml) than those treated with indomethacin (366±37) and saline (435±13). NS-398-treated animals produced more urine ([A], 18±4; [B], 12±3; [C], 13±3 ml/6 – 24 h) and had fewer episodes of respiratory distress ([A], 12%; [B], 57%; [C], 71% ) . It is suggested that selective COX-2 (rather than non-selective COX) inhibition attenuates the systemic inflammatory response to pancreatic injury and that this may be another step towards optimizing therapy in severe AP.