Cytokine profile in colonic mucosa of ulcerative colitis correlates with disease activity and response to granulocytapheresis.

Abstract

The aim of this study was to clarify the correlation between cytokine profile in colonic mucosa with disease activity and response to granulocytapheresis (GCAP) in patients with ulcerative colitis (UC), using a reliable, reproducible quantitative method. Colonoscopic biopsies of inflamed colonic mucosa (16 patients, 21 cases) and uninflamed colonic mucosa (25 patients, 33 cases) were obtained from UC patients. Messenger (m)RNA was extracted and subjected to realtime polymerase chain reaction for quantitative measurement of interleukin (IL)-12, interferon-gamma, tumor necrosis factor-alpha, IL-4, IL-8, and IL-18 mRNAs. In seven patients with high disease activity despite prednisolone (PSL) treatment (> or = 20 mg/day), one course of GCAP was conducted, and pre- and post-GCAP cytokine profiles were determined. In inflamed colonic mucosa of UC patients, three cytokine profiles were observed: 1) high expression of interferon-gamma, tumor necrosis factor-alpha, and IL-4 mRNAs but low expression of IL-8 mRNA; 2) high expression of IL-8 mRNA and low expression of others; and 3) low expression of all cytokines examined. Inflamed colonic mucosa of patients with high disease activity showed the second pattern. Inflamed colonic mucosa of patients who were not treated with PSL and who had low disease activity showed the first pattern, whereas those on high-dose PSL exhibited the second pattern. IL-8 mRNA was significantly higher in inflamed UC samples than in uninflamed samples. GCAP was effective in five of seven PSL-resistant patients (71.4%). IL-8 was the only cytokine that correlated with effectiveness of GCAP. Compared with GCAP nonresponders, responders had significantly higher IL-8 mRNA before GCAP and showed marked reduction of IL-8 mRNA after GCAP. IL-8 mRNA was significantly increased in inflamed mucosa of UC. Patients with high IL-8 mRNA expression in colonic mucosa despite PSL treatment were responsive to GCAP. Therefore, quantitative measurement of mucosal IL-8 mRNA may be useful in predicting the response to GCAP.