Altered leukotriene b₄ metabolism in colonic mucosa with inflammatory bowel disease

Background: ωOxidation 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 ωoxidation 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 ωoxidative metabolites by high-performance liquid chromatography. Results: The rate of LTB₄ ωoxidation was comparable to the rate of its biosynthesis. The metabolic ratio was significantly decreased in inflamed mucosa with ulcerative colitis. Conclusions: LTB₄ ωhydroxylase 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 ωhydroxylase activity and increased 5-lipoxygenase activity.