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

Background & Aims: This study demonstrates a significant role for cyclooxyg enase (COX)-2 and prostanoid production as mechanisms for surgically induce d postoperative ileus. Methods: Rats, COX-2(+/+), and COX-2(-/-) mice under went simple intestinal manipulation. Reverse-transcription polymerase chain reaction and immunohistochemistry were used to detect and localize COX-2 e xpression. 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 i n vivo. Results: The data show that intestinal manipulation induces COX-2 m essenger RNA and protein within resident muscularis macrophages, a discrete subpopulation of myenteric neurons and recruited monocytes. The manipulati on-induced increase in COX-2 expression resulted in significantly elevated prostaglandin levels within the circulation and peritoneal cavity. The sour ce of these prostanoids could be directly attributed to their release from the inflamed muscularis externa. As a consequence of the molecular up-regul ation of COX-2, we observed a decrease in in vitro jejunal circular muscle contractility and gastrointestinal transit, both of which could be alleviat ed pharmacologically with selective COX-2 inhibition. These studies were co rroborated with the use of COX-2(-/-) mice. Conclusions: Prostaglandins, th rough the induction of COX-2, are major participants in rodent postoperativ e ileus induced by intestinal manipulation.