Clinical Research
Copyright ©2006 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Jun 7, 2006; 12(21): 3386-3392
Published online Jun 7, 2006. doi: 10.3748/wjg.v12.i21.3386
Rectal nitric oxide as biomarker in the treatment of inflammatory bowel disease: Responders versus nonresponders
Tryggve Ljung, Sofie Lundberg, Mark Varsanyi, Catharina Johansson, Peter T Schmidt, Max Herulf, Jon O Lundberg, Per M Hellström
Tryggve Ljung, Sofie Lundberg, Mark Varsanyi, Catharina Johansson, Per M Hellström, Peter Thelin Schmidt, Department of Gastroenterology and Hepatology, Karolinska University Hospital, Site Solna, Stockholm, Sweden
Max Herulf, Jon O Lundberg, Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden
Supported by the Swedish Research Council, Novo Nordisk and the Bengt Ihre fund
Correspondence to: Tryggve Ljung, MD, PhD, Department of Gastroenterology and Hepatology, Karolinska University Hospital, Site Solna, SE-171 76 Stockholm, Sweden. tryggve.ljung@hotmail.com
Telephone: +46-8-51773877 Fax: +46-8-51772058
Received: October 12, 2005
Revised: October 28, 2005
Accepted: November 10, 2005
Published online: June 7, 2006
Abstract

AIM: To explore rectal nitric oxide (NO) as biomarker of treatment response in ulcerative colitis (UC) and Crohn’s disease (CD), and examine relationships between rectal NO, mucosal expression of NO synthases (NOS), and pro-inflammatory cytokines.

METHODS: Twenty-two patients with UC and 24 with CD were monitored during steroid treatment. Rectal NO levels were measured and clinical activities were assessed on days 1, 3, 7 and 28. Mucosal presence of NOS and pro-inflammatory cytokines were analyzed by immunohistochemistry and RT-PCR.

RESULTS: Active UC and CD displayed markedly increased rectal NO levels (10 950 ± 7610 and 5 040 ± 1 280 parts per billion (ppb), respectively) as compared with the controls (154 ± 71 ppb, P < 0.001). Rectal NO correlated weakly with disease activity in both UC and CD (r = 0.34 for UC and r = 0.48 for CD, P < 0.01). In 12 patients, a steroid-refractory course led to colectomy. These patients had only slightly increased NO levels (UC: 620 ± 270 ppb; CD: 1260 ± 550 ppb) compared to those with a therapeutic response (UC: 18 860 ± 530 ppb, P < 0.001; CD: 10 060 ± 3200 ppb, P < 0.05).

CONCLUSION: Rectal NO level is a useful biomarker of treatment response in IBD as low NO levels predicts a poor clinical response to steroid treatment.

Keywords: Crohn’s disease; Cytokines; Nitric oxide; Steroids; Ulcerative colitis