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.