Altered Leukotriene B4 Metabolism in Colonic Mucosa with Inflammatory Bowel Disease

Background: ω-Oxidation is regarded as the major pathway for leukotriene B4 (LTB4) metabolism. Very little is known about it in colonic mucosa with inflammatory bowel disease (IBD). Methods: We investigated the metabolic ratio of ω-oxidation to LTB4 biosynthesis in colonic mucosa from patients with IBD and control subjects. After incubation of colonic mucosa with 14C-arachidonic acid and ionophore A23187, we separated LTB4 and its ω-oxidative metabolites by high-performance liquid chromatography. Results: The rate of LTB4 ω-oxidation was comparable to the rate of its biosynthesis. The metabolic ratio was significantly decreased in inflamed mucosa with ulcerative colitis. Conclusions: LTB4 ω-hydroxylase activity is an important factor in regulating LTB4 level in colonic mucosa, and the increased LTB4 level in inflamed mucosa with IBD, especially ulcerative colitis, is caused by decreased LTB4 ω-hydroxylase activity and increased 5-lipoxygenase activity.