Increase in cyclooxygenase-2 and nitric oxide-synthase-2 mRNAs in pouchitis without modification of inducible isoenzyme heme-oxygenase-1

OBJECTIVES: The pathophysiology of pouchitis occurring after ileal pouch-an al anastomosis remains controversial. Prostaglandins and nitric oxide synth esized in excess by cyclooxygenase-2 and nitric oxide synthase-2 are though t to be involved in the inflammatory process. Because heme oxygenase-l, by its antioxidant properties, could modulate inflammatory reaction, we analyz ed mRNAs of the three enzymes (cyclooxygenase-2, nitric oxide synthase-2, a nd heme oxygenase-l) in patients with ileal pouch-anal anastomosis. METHODS: Endoscopic biopsies were obtained in eight patients with normal il eal pouch-anal anastomosis, in eight patients with pouchitis, and in normal ileum of six healthy subjects. A relative quantitative RT-PCR was performe d to determine the levels of cyclooxygenase-2, nitric oxide synthase-2, and heme oxygenase-l mRNAs. RESULTS: Cyclooxygenase-2 and nitric oxide synthase-2 mRNAs were increased both in normal ileal pouch-anal anastomosis and in pouchitis, compared with healthy subjects. Pouchitis disease activity index was correlated with mRN A levels of cyclooxygenase-2 (r = 0.71; p < 0.01) and nitric oxide synthase -2 (r = 0.51; p < 0.05). Heme oxygenase-l mRNA levels were not significantl y different in patients versus healthy subjects. CONCLUSIONS: The increase in cyclooxygenase-2 and nitric oxide synthase-2 m RNA levels both in pouchitis and normal ileal pouch-anal anastomosis demons trates that a latent inflammatory process occurs in the ileal pouch mucosa. This inflammatory process was not found to be associated with an induction of heme oxygenase mRNA, a possible regulator of the inflammatory response. (C) 2001 by Am. Coll. of Gastroenterology.