Prostanoid production via COX-2 as a causative mechanism of rodent postoperative ileus

Background & Aims: This study demonstrates a significant role for cyclooxygenase (COX)-2 and prostanoid production as mechanisms for surgically induced postoperative ileus. Methods: Rats, COX-2^+/+, and COX-2^-/- mice underwent simple intestinal manipulation. Reverse-transcription polymerase chain reaction and immunohistochemistry were used to detect and localize COX-2 expression. Prostaglandin levels were measured from serum, peritoneal lavage fluid, and muscularis culture media. Jejunal circular muscle contractions were measured in an organ bath, and gastrointestinal transit was measured in vivo. Results: The data show that intestinal manipulation induces COX-2 messenger RNA and protein within resident muscularis macrophages, a discrete subpopulation of myenteric neurons and recruited monocytes. The manipulation-induced increase in COX-2 expression resulted in significantly elevated prostaglandin levels within the circulation and peritoneal cavity. The source of these prostanoids could be directly attributed to their release from the inflamed muscularis externa. As a consequence of the molecular up-regulation of COX-2, we observed a decrease in in vitro jejunal circular muscle contractility and gastrointestinal transit, both of which could be alleviated pharmacologically with selective COX-2 inhibition. These studies were corroborated with the use of COX-2^-/- mice. Conclusions: Prostaglandins, through the induction of COX-2, are major participants in rodent postoperative ileus induced by intestinal manipulation.