Role of inducible cyclooxygenase and prostaglandins in Clostridium difficile toxin A-induced secretion and inflammation in an animal model

Cyclooxygenase (Cox)-2 expression and inhibition were investigated in a rab bit ileal loop model of Clostridium difficile colitis and diarrhea. Intesti nal tissue stimulated with C. difficile toxin A showed up-regulation of Cox -2 expression in lamina propria macrophages and elevated prostaglandin leve ls. Toxin A-stimulated loops exhibited severe inflammation and increased se cretory volume. Celecoxib, a specific Cox-2 inhibitor, significantly reduce d toxin A-induced prostaglandin production. Furthermore, celecoxib (greater than or equal to0.02 mg/mL) blocked both histologic damage (mean histologi c grade, 1.25 vs. 3.44 in rabbits receiving toxin A alone; P < .0005) and s ecretion (volume: length ratio, 0.18 vs. 0.72 in those receiving toxin A al one; P = .002) in toxin A-stimulated loops in a dose-related manner. Thus, toxin A induced expression of Cox-2 in the host, and prostaglandins produce d through Cox-2 were involved in the mediation of the increased secretion o f electrolytes and water and the inflammatory response induced by toxin A.