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Serum and Colonic Mucosal Immune Markers in Irritable Bowel Syndrome

Chang, Lin MD1, 2; Adeyemo, Mopelola BS1, 2; Karagiannidis, Iordanis PhD2, 3; Videlock, Elizabeth J MD1, 2, 11; Bowe, Collin BS2, 3; Shih, Wendy MPH4; Presson, Angela P PhD4; Yuan, Pu-Qing1, 3, 5; Cortina, Galen MD6; Gong, Hua MD, PhD7; Singh, Sharat PhD7; Licudine, Arlene LVN1, 2; Mayer, Minou LCSW1, 2; Tache, Yvette PhD1, 3, 5; Pothoulakis, Charalabos MD2, 3; Mayer, Emeran A MD1, 2, 8, 9, 10

American Journal of Gastroenterology: February 2012 - Volume 107 - Issue 2 - p 262–272
doi: 10.1038/ajg.2011.423
Functional GI Disorders
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OBJECTIVES: Low-grade colonic mucosal inflammation has been postulated to have an important role in the pathophysiology of irritable bowel syndrome (IBS). The objectives of this study were (i) to identify serum and tissue-based immunological and neuroendocrine markers associated with mucosal inflammation in male (M) and female (F) patients with non-post-infectious IBS (non-PI-IBS) compared with healthy controls and (ii) to assess possible correlations of such markers with IBS symptoms.

METHODS: Sigmoid mucosal biopsies were obtained from 45 Rome II positive IBS patients without a history of PI-IBS (26 F, 35.5% IBS-C, 33.3% IBS-D, 31.1% IBS-A/M) and 41 healthy controls (22 F) in order to measure immunological markers (serum cytokine levels, colonic mucosal mRNA levels of cytokines, mucosal immune cell counts) and neuroendocrine markers associated with mucosal inflammation (corticotropin releasing factor- and neurokinin (NK)-related ligands and receptors, enterochromaffin cells). Symptoms were measured using validated questionnaires.

RESULTS: Of all the serum and mucosal cytokines measured, only interleukin-10 (IL-10) mRNA expression showed a group difference, with female, but not male, patients showing lower levels compared with female controls (18.0±2.9 vs. 29.5±4.0,P=0.006). Mucosal mRNA expression of NK-1 receptor was significantly lower (1.15±0.19 vs. 2.66±0.56,P=0.008) in female, but not male, patients compared with healthy controls. No other significant differences were observed.

CONCLUSIONS: Immune cell counts and levels of cytokines and neuropeptides that are associated with inflammation were not significantly elevated in the colonic mucosa of non-PI-IBS patients, and did not correlate with symptoms. Thus, these findings do not support that colonic mucosal inflammation consistently has a primary role in these patients. However, the finding of decreased IL-10 mRNA expression may be a possible biomarker of IBS and warrants further investigation.

1 Center for Neurobiology of Stress, University of California, Los Angeles, California, USA

2 Department of Medicine, University of California, Los Angeles, California, USA

3 Inflammatory Bowel Disease Center, Department of Medicine, University of California, Los Angeles, California, USA

4 Department of Biostatistics, University of California, Los Angeles, California, USA

5 VA GLA Healthcare System, Los Angeles, California, USA

6 Department of Pathology, University of California, Los Angeles, California, USA

7 Prometheus Laboratories, San Diego, California, USA

8 Department of Physiology, University of California, Los Angeles, California, USA

9 Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, California, USA

10 Brain Research Institute, David Geffen School of Medicine, University of California, Los Angeles, California, USA

11 Department of Medicine, Beth Israel Deconess Medical Center, Boston, Massachusetts, USA

Correspondence: Lin Chang, MD, Center for Neurobiology of Stress, University of California, 10833 Le Conte Avenue, CHS 42-210, Los Angeles, California 90095-7378, USA. E-mail: linchang@ucla.edu

Received 21 April 2011; accepted 29 August 2011

published online 13 December 2011

© The American College of Gastroenterology 2012. All Rights Reserved.
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