Abstract
Immune activation may underlie the pathogenesis of irritable bowel syndrome (IBS), but the evidence is conflicting. We examined whether peripheral CD4+ T-cells from IBS patients demonstrated immune activation and changes in cytokine production. To gain mechanistic insight, we examined whether immune activation correlated with psychological stress and changing symptoms over time. IBS patients (n = 29) and healthy volunteers (HV; n = 29) completed symptom and psychological questionnaires. IBS patients had a significant increase in CD4+ T-cells expressing the gut homing marker integrin β7 (p = 0.023) and lymphoid marker CD62L (p = 0.026) compared to HV. Furthermore, phytohaemagglutinin stimulated CD4+ T-cells from IBS-D patients demonstrated increased TNFα secretion when compared to HV (p = 0.044). Increased psychological scores in IBS did not correlate with TNFα production, while stress hormones inhibited cytokine secretion from CD4+ T-cells of HV in vitro. IBS symptoms, but not markers of immune activation, decreased over time. CD4+ T-cells from IBS-D patients exhibit immune activation, but this did not appear to correlate with psychological stress measurements or changing symptoms over time. This could suggest that immune activation is a surrogate of an initial trigger and/or ongoing parallel peripheral mechanisms.
Highlights
We chose to concentrate on TNFα, IL-6, and IL-10 since previous reports have demonstrated evidence for the existence of TNFα, IL-6 and IL-10 gene polymorphisms in IBS21,22, and these cytokines have been well studied in the serum[2,3,10,12,17,18] and peripheral blood mononuclear (PBMC) populations[16,23,24,25,26,27,28] in irritable bowel syndrome (IBS)
We examined the CD4+ T-cell population from the total PBMC population, rather than isolated CD4+ T-cells, as the PBMC population more closely resembles the population in circulation in vivo and because these cells had been least subjected to manipulation, since this may alter the expression of cell surface markers such as integrins[33,34]
This study examined whether immune activation is present in IBS and if so, whether it is mechanistically linked to factors underlying psychological distress
Summary
Studies have examined immune activation at a particular time point, longitudinal studies have been lacking, despite the fact that IBS is a chronic disorder and immune activation could play a role in sustaining symptoms. There is an increase in gut-homing T-cells[11,20] in the peripheral blood in IBS, suggesting increased adaptive immune activation. We first sought to determine whether there was evidence of immune activation in IBS, by examining peripheral blood CD4+ T-cell homing and stimulated cytokine production as a sensitive assay of immune activation. We assessed whether CD4+ T-cell immune activation could be related to signalling from the central nervous system, by examining the relationship between CD4+ T-cell activation, chronic gut symptoms, psychological distress and stress hormones. We correlated changes in symptoms over time with cytokines released by stimulated peripheral CD4+ T-cells. We chose to concentrate on TNFα, IL-6, and IL-10 since previous reports have demonstrated evidence for the existence of TNFα, IL-6 and IL-10 gene polymorphisms in IBS21,22, and these cytokines have been well studied in the serum[2,3,10,12,17,18] and peripheral blood mononuclear (PBMC) populations[16,23,24,25,26,27,28] in IBS
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