Mucosal factors inducing neutrophil movement in ulcerative colitis: the role of interleukin 8 and leukotriene B4.

Abstract

The movement of neutrophils into the colonic mucosa in ulcerative colitis is induced by chemokines including interleukin 8 (IL8) and leukotriene B4 (LTB4). To compare the ability of mucosa from ulcerative colitis patients and controls to stimulate neutrophil movement, to define the contribution of LTB4 to this, and to define the relative biological importance of LTB4 and IL8. Resected mucosa was obtained from seven control patients and 10 patients with ulcerative colitis. Mucosal homogenate supernatants were used to stimulate isolated neutrophils and the effect assessed by the neutrophil shape change response. Responses were inhibited with either the LTB4 receptor antagonist SC41930- or neutralising anti-IL8 antibody. LTB4 was extracted and assayed by RIA. Homogenate supernatants from inflamed mucosa were more bioactive (median 1.2 mg/ml-1 induced 50% response) than those from uninflamed mucosa (4.25 mg/ml-1 induced 50% response; difference 2.8 mg/ml-1 (96.5% CI 0.5 to 6.1, p < 0.05). Maximal inhibition by SC41930 of the response was significantly greater in inflamed mucosa (54% median) than in uninflamed mucosa (34%). This inhibition correlated with the level of immunoreactive LTB4 (r = 0.78). Anti-IL8 reduced bioactivity of homogenate supernatants from inflamed mucosa (at 1:10 dilution) by 11.4% (IQR 1.2 to 51.8, p = 0.021) whereas SC41930 reduced it by 54.8% (35.6 to 77.5, p = 0.008). Inflamed colonic mucosa releases more neutrophil movement inducing bioactivity than uninflamed mucosa, and has greater LTB4 dependent activity. It yields both IL8 and LTB4 dependent activity but greater LTB4 dependent activity.