T2072 Colonic Mucosal Inflammation is Unlikely to Play a Primary Role in Irritable Bowel Syndrome

Abstract

Introduction: An enhanced mucosal immune or inflammatory response has been postulated to play a key role in the pathophysiology of IBS. Previous studies have reported an increase in serum cytokines and colonic mucosal lymphocyte and mast cell counts in IBS patients vs. healthy controls (HCs), but data are inconsistent and limited. Aims: 1) To compare inflammatory markers in the blood and colonic mucosa in IBS and HCs, 2) To determine if these measures are affected by sex, and 3) To explore if these measures are related to IBS symptoms.Methods: Male (M) and female (F) Rome positive IBS patients with stable disease activity and HCs underwent a sigmoidoscopy with colon biopsies (taken at 30 cm from the anal verge). Blood samples were also collected. The following was measured: 1) serum levels of cytokines (IL-1β, IL-6, IL-8, IL-10, and TNF-α), 2) mucosal mRNA levels of the same cytokines, CRF, and CRF1 receptor using real-time PCR, and 3) lymphocyte and mast cell counts per total biopsy area using an automated system. All subjects completed questionnaires assessing GI and non-GI symptoms. Results: 45 IBS patients (26F, 19M) and 41 agematched HCs (22F, 19M) were studied. IBS subtypes were 34% IBS-C, 34% IBS-D, and 32% IBS-M/A. None of the IBS patients had documented post-infectious IBS. Overall, there were no statistically significant differences in any of the measured inflammatory markers between IBS patients and HCs. However, group differences were seen amongst female subjects. Compared to healthy women, female IBS had a small but significant mean increase in serum level of the pro-inflammatory cytokine TNF-α (4.4±0.08 vs. 4.1±0.06 pg/ml, p= 0.046). They also had lower mucosal mRNA levels of the anti-inflammatory cytokine IL-10 compared to HCs (4.9±0.1 vs. 5.5±0.2, p=0.02). However, neither finding maintained statistical significance when corrected for multiple comparisons. Serum cytokine levels did not correlate with their respective mucosal cytokine mRNA levels (p=NS). There were no significant differences in CRF colonic mucosal expression or cell counts between IBS and controls. Serum IL-10 levels (r=-0.44, p = 0.006) and colonic mucosal CRF expression (r=0.45, p=0.003) negatively correlated with current symptom ratings. Conclusion: Taken together, the lack of strong and significant differences in mucosal and serum immune markers between IBS andHCs argues against the presence of a predominant proinflammatory response within the colonic mucosa in IBS. Further studies are needed to determine if an immune disturbance plays a more significant role in women with IBS, and if immune markers are associated with symptom flares in IBS.