Involvement of Corticotropin-Releasing Factor and Receptors in Immune Cells in Irritable Bowel Syndrome

Many cross-sectional surveys have reported the prevalence of irritable bowel syndrome (IBS), but there have been no recent systematic review of data from all studies to determine its global prevalence and risk factors. MEDLINE, EMBASE, and EMBASE Classic were searched (until October 2011) to identify population-based studies that reported the prevalence of IBS in adults (≥15 years old); IBS was defined by using specific symptom-based criteria or questionnaires. The prevalence of IBS was extracted for all studies and based on the criteria used to define it. Pooled prevalence, according to study location and certain other characteristics, odds ratios (ORs), and 95% confidence intervals (CIs) were calculated. Of the 390 citations evaluated, 81 reported the prevalence of IBS in 80 separate study populations containing 260,960 subjects. Pooled prevalence in all studies was 11.2% (95% CI, 9.8%-12.8%). The prevalence varied according to country (from 1.1% to 45.0%) and criteria used to define IBS. The greatest prevalence values were calculated when ≥3 Manning criteria were used (14%; 95% CI, 10.0%-17.0%); by using the Rome I and Rome II criteria, prevalence values were 8.8% (95% CI, 6.8%-11.2%) and 9.4% (95% CI, 7.8%-11.1%), respectively. The prevalence was higher for women than men (OR, 1.67; 95% CI, 1.53-1.82) and lower for individuals older than 50 years, compared with those younger than 50 (OR, 0.75; 95% CI, 0.62-0.92). There was no effect of socioeconomic status, but only 4 studies reported these data. The prevalence of IBS varies among countries, as well as criteria used to define its presence. Women are at slightly higher risk for IBS than men. The effects of socioeconomic status have not been well described. Copyright © 2012 AGA Institute. Published by Elsevier Inc. All rights reserved.

The mechanisms underlying abdominal pain perception in irritable bowel syndrome (IBS) are poorly understood. Intestinal mast cell infiltration may perturb nerve function leading to symptom perception. We assessed colonic mast cell infiltration, mediator release, and spatial interactions with mucosal innervation and their correlation with abdominal pain in IBS patients. IBS patients were diagnosed according to Rome II criteria and abdominal pain quantified according to a validated questionnaire. Colonic mucosal mast cells were identified immunohistochemically and quantified with a computer-assisted counting method. Mast cell tryptase and histamine release were analyzed immunoenzymatically. Intestinal nerve to mast cell distance was assessed with electron microscopy. Thirty-four out of 44 IBS patients (77%) showed an increased area of mucosa occupied by mast cells as compared with controls (9.2% +/- 2.5% vs. 3.3 +/- 0.8%, respectively; P < 0.001). There was a 150% increase in the number of degranulating mast cells (4.76 +/- 3.18/field vs. 2.42 +/- 2.26/field, respectively; P = 0.026). Mucosal content of tryptase was increased in IBS and mast cells spontaneously released more tryptase (3.22 +/- 3.48 pmol/min/mg vs. 0.87 +/- 0.65 pmol/min/mg, respectively; P = 0.015) and histamine (339.7 +/- 59.0 ng/g vs. 169.3 +/- 130.6 ng/g, respectively; P = 0.015). Mast cells located within 5 microm of nerve fibers were 7.14 +/- 3.87/field vs. 2.27 +/- 1.63/field in IBS vs. controls (P < 0.001). Only mast cells in close proximity to nerves were significantly correlated with severity and frequency of abdominal pain/discomfort (P < 0.001 and P = 0.003, respectively). Colonic mast cell infiltration and mediator release in proximity to mucosal innervation may contribute to abdominal pain perception in IBS patients.

Post-dysenteric irritable bowel syndrome (PD-IBS) develops in up to 25% of patients following Campylobacter enteritis. Our aim was to define the pathological basis of this subgroup of IBS. Twenty one patients (group 1) underwent serial rectal biopsy and gut permeability testing following acute Campylobacter enteritis as did 10 PD-IBS patients (group 2) and 12 asymptomatic controls. In group 1, enteroendocrine cell (EC) numbers were markedly increased initially and at six and 12 weeks (p<0.001) compared with controls. Gut permeability, as assessed by the lactulose/mannitol ratio, was significantly elevated, initially and at 12 weeks (p<0.005). CD3, CD4, and CD8 lymphocyte counts in the lamina propria and intraepithelial lymphocytes (IEL) were significantly increased initially compared with controls. At visit 1, EC numbers were positively correlated with CD3 counts (r=0.6, p=0.01). At one year, seven subjects (five with persistent loose stools) had rectal biopsies which showed significantly elevated EC, CD3, and IEL counts. In group 2, EC and IEL counts were significantly increased compared with controls (p<0.001), as was gut permeability (p<0.01). Increased EC, T lymphocytes, and gut permeability are acute changes following Campylobacter enteritis which can persist for more than a year and may contribute to PD-IBS.