Serum and Colonic Mucosal Immune Markers in Irritable Bowel Syndrome

Abstract

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.

Editorial: Abnormal Immune Regulation and Low-Grade Inflammation in IBS: Does One Size Fit All?

“…In conclusion, the study by Chang et al ( 22 ) provides another piece of evidence, which supports a state of abnormal immune regulation in IBS. It is attractive to speculate that in aff ected individuals, luminal insults such as enteric infections, dysbiosis, or environmental exposures might serve as the hand that strikes the match to induce low-grade infl ammation, and in some, the symptoms of IBS.…”

“…Elevated proinfl ammatory cytokines from peripheral blood mononuclear cells in the basal period and aft er stimulation with lipopolysaccharides has been shown in IBS-diarrhea ( 14 ). In contrast, other investigators could from men and women with IBS ( 22 ). Th eir well-characterized IBS population was recruited from a US specialty clinic and the surrounding community.…”

Validation of the Rome III Criteria for the Diagnosis of Irritable Bowel Syndrome in Secondary Care

“…One possibility is to also evaluate patients with colonoscopy and relevant biological markers, as well as obtain a detailed symptom history. 47,49,50 The symptom data can then be compared with the biological markers and colonoscopy results using statistical techniques, such as latent class analysis and Bayesian analysis. 51 These techniques can classify patients into categories based on the underlying structure of the data, without relying on a gold standard.…”

The Overlap in the Genetic Pathogenesis of Ulcerative Colitis and Irritable Bowel Syndrome

“…Yet, only a few studies have addressed the association of IL-10 and IL-10 gene polymorphisms in IBS. Chang et al [7] reported lower colonic mucosal mRNA expression of IL-10 in IBS females compared with healthy females. Moreover, several IL-10 genotypes were less prevalent in patients with IBS compared with that of control groups [8].…”