Role of eicosanoids as mediators of inflammation in inflammatory bowel disease

An unknown initiating event in inflammatory bowel disease (IBD) activates the immune system,'which is followed by infiltration of the intestinal mucosa with inflammatory cells and the production of soluble mediators of inflammation. These mediators of inflammation include the metabolites of arachidonic acid. The results of research on arachidonic acid metabolites are reviewed, and it is concluded that the major arachidonic metabolites in human IBD mucosa are the lipoxygenase products leukotriene B₄ (LTB₄) and 5-hydroxy-6,8,l 1,14-eicosatetraenoic acid. These metabolites are found in much higher concentrations in mucosa from patients with IBD than from healthy controls. Significantly more chemotactic activity is found in IBD mucosa than in healthy mucosa, and most of this activity is attributable to LTB₄. Enhanced synthesis of LTB₄ could account for much of the inflammatory response in IBD. Inhibition of the lipoxygenase pathway could be the mechanism that accounts for the therapeutic efficacy of mesalazine.