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Quantitive Cytokine mRNA Expression Profiles in the Colonic Mucosa of Patients with Steroid Naïve Ulcerative Colitis During Active and Quiescent Disease

Matsuda, Reikei MD1; Koide, Tomoko MD2; Tokoro, Chikako MD2; Yamamoto, Tsuyoshi MD1; Godai, Ten'i MD4; Morohashi, Taiki MD3; Fujita, Yuji MD1; Takahashi, Daisuke MD1; Kawana, Ichiro MD2; Suzuki, Shinichiro MD4; Umemura, Satoshi MD5

doi: 10.1002/ibd.20759
Original Article: Original Basic Science Articles

Background: Cytokines have validated roles in the immunopathogenesis of inflammatory bowel disease (IBD). This study was to investigate the expressions of tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-8, and IL-10 mRNAs in the colonic mucosa of patients with ulcerative colitis (UC) during active and quiescent UC.

Methods: At colonoscopy, biopsies were taken from inflamed and non-inflamed mucosa of patients with steroid-naive UC (n = 15), non-IBD inflammatory colitis controls (ICC, n = 6), and non-colitis controls (NCC, n = 14). The presence of extensive mononuclear cells and neutrophils infiltrate in the lamina propria, cryptitis, and epithelial damage defined an inflammatory lesion in the mucosa. Quantitative cytokine mRNA expressions in biopsies were measured by real-time polymerase chain reaction (PCR).

Results: Of 15 UC patients, 3 remitted with 5-aminosalicylate and 11 received granulocytapheresis; of these, 10 remitted. At baseline, IL-6, IL-8, TNF-α, and IL-10 mRNAs were high in inflamed mucosa compared with NCC (P < 0.01). In active UC, IL-6, IL-8 and IL-10 mRNAs were high compared with non-inflamed mucosa (P = 0.03, P = 0.03, P < 0.05, respectively). Both TNF-α mRNA (P = 0.03) and IL-6 mRNA (P = 0.04) were higher in UC compared with ICC. Even in non-inflamed mucosa, IL-8 and TNF-α mRNA expressions were high compared with NCC. Both IL-6 and IL-8 mRNAs decreased to normal levels after granulocytapheresis.

Conclusions: During active UC, all 4 cytokine mRNA levels were high; only IL-6 and IL-8 mRNAs decreased to normal levels during remission. IL-8 mRNA was high even at sites of endoscopically quiescent UC during active disease. Steroid naïve patients respond well to granulocytapheresis.

1Department of Internal Medicine, Fujisawa Shounandai Hospital, Fujisawa, Japan

2Department of Gastroenterology, Yokohama City University School of Medicine, Yokohama, Japan

3Department of Gastroenterology, Omori Red Cross Hospital, Ohta-Ku, Tokyo, Japan

4Department of Surgery, Fujisawa Shounandai Hospital, Fujisawa, Japan

5Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Japan

Reprints: Reikei Matsuda, MD, Department of Internal Medicine, Fujisawa Shounandai Hospital, 2345 Takakura Fujisawa Kanagawa 2520802, Japan


Received for publication August 12 2008; Accepted August 17 2008

Published online 22 October 2008 in Wiley InterScience (

© Crohn's & Colitis Foundation of America, Inc.
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