Chemotactic activity in inflammatory bowel disease

An important histologic feature of inflammatory bowel disease (IBD) is infiltration of the colonic mucosa with neutrophils. To investigate the nature of the chemotactic agents responsible for this infiltration, colonic mucosa from three normals and nine patients with inflammatory bowel disease (seven ulcerative colitis, two Crohn's colitis) was assayed for chemotactic activity for human neutrophilsin vitro in a Boyden chamber. There was more (>10-fold more) chemotactic activity in homogenates of inflammatory bowel disease mucosa than in homogenates of normal colonic mucosa. Analysis of the chemotactic activity in the inflammatory bowel disease mucosa revealed that most was lipid extractable. Moreover, when the lipid extract was fractionated by reverse-phase high-pressure liquid chromatography, the only fraction with significant chemotactic activity was the fraction that coeluted with leukotriene B₄. The chemotactic response to IBD mucosa was blocked by anti-LTB₄ antisera. The amount of chemotactic activity in lipid extracts of different inflammatory bowel disease specimens correlated well with the concentration of leukotriene B₄ measured by UV absorbance (250 ng/g of mucosa). These data suggest that leukotriene B₄ is an important stimulus to neutrophil chemotaxis in inflammatory bowel disease and, thus, may play a major role in the amplification of the inflammatory response in this condition.This work is supported by a grant from the National Foundation for Ileitis and Colitis and grant AM-33165 from the National Institutes of Health.