Objectives: The pathophysiology of pouchitis occurring after ileal pouch-anal anastomosis remains controversial. Prostaglandins and nitric oxide synthesized in excess by cyclooxygenase-2 and nitric oxide synthase-2 are thought to be involved in the inflammatory process. Because heme oxygenase-1, by its antioxidant properties, could modulate inflammatory reaction, we analyzed mRNAs of the three enzymes (cyclooxygenase-2, nitric oxide synthase-2, and heme oxygenase-1) in patients with ileal pouch-anal anastomosis.
Methods: Endoscopic biopsies were obtained in eight patients with normal ileal pouch-anal anastomosis, in eight patients with pouchitis, and in normal ileum of six healthy subjects. A relative quantitative RT-PCR was performed to determine the levels of cyclooxygenase-2, nitric oxide synthase-2, and heme oxygenase-1 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 mRNA levels of cyclooxygenase-2 (r = 0.71; p < 0.01) and nitric oxide synthase-2 (r = 0.51; p < 0.05). Heme oxygenase-1 mRNA levels were not significantly different in patients versus healthy subjects.
Conclusions: The increase in cyclooxygenase-2 and nitric oxide synthase-2 mRNA levels both in pouchitis and normal ileal pouch-anal anastomosis demonstrates 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.