n-3 Fatty acids in the treatment of ulcerative colitis

Abstract

Ulcerative colitis is a chronic inflammatory disease of the large bowel of unknown etiology. The inflammation is generally confined to the mucosal layers, resulting in extensive superficial ulceration. Antiinflammatory drugs are helpful in treating this condition, as are drugs that reduce the immune response such as azathioprine and 6-mercaptopurine. Fish oil n-3 polyunsaturated fatty acids (PUFAs), eicosapentaenoic (EPA) and docosahexaenoic acids (DHA), alter the production of leukotrienes by the lipoxygenase pathway and prostaglandins via the cyclooxygenase pathway. The major fatty acid for leukotriene synthesis is arachidonic acid (AA), which is the substrate for leukotriene B₄ (LTB₄). This cytokine is formed primarily by inflammatory cells [1] and its main role in the inflammatory reaction appears to be recruitment of neutrophils from the circulation to the inflamed tissue. When EPA is the substrate for this pathway, however, the product is leukotriene B₅ (LTB₅) which has only 10% of the activity of LTB₄ with regards to inducing neutrophil aggregation [2]. Furthermore, when AA and EPA are incubated together the production of LTB₄ is reduced by 68% [2]. In humans consuming a diet supplemented with fish oil, the 5-lipoxygenase pathway in both neutrophils and monocytes was reduced, and the adherence of neutrophils to vessel endothelium was inhibited completely. Additionally these neutrophils displayed less chemotactic response to LTB₄ [3].