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Type: Conference item
Title: TNF-alpha from gut homing memory T cells and monocytes sensitises colonic sensory afferents in IBS-D
Author: Hughes, P.A.
Bird, D.
Brierley, S.M.
Persson, J.
Moretta, M.
Blackshaw, L.A.
Zola, H.
Krumbiegel, D.
Andrews, J.M.
Citation: Neurogastroenterology and Motility. Supplement, 2012, vol.24, iss.Suppl. 2, pp.24-24
Issue Date: 2012
Series/Report no.: Oral Presentations: OP-05 Basic and Translational Plenary Session
ISSN: 1743-3150
Conference Name: Joint International Neurogastroenterology and Motility Meeting (6 Sep 2012 - 8 Sep 2012 : Bologna, Italy)
Statement of
P. Hughes, D. Bird, S. Brierley, J. Persson, M. Moretta, L. A. Blackshaw, H. Zola, D.Krumbiegel, And J. Andrews
Abstract: Objective: There is increasing evidence that the symptoms of Irritable Bowel Syndrome (IBS) result from alterations in the immune system, however the immune cell types and mediators involved remain controversial. We have previously shown PBMC supernatants from IBS-D patients sensitise colonic sensory afferents and contain elevated amounts of TNF-a, IL-6and IL-1b (1,2).Methods: PBMC were isolated from 36 HS, 20 IBS-D and 15 IBS-C patients, cultured overnight and supernatants pooled according to IBS subtype. The functional effects PBMC supernatants and individual cytokines have on pelvic serosal colo-rectal afferents were determined using single unit electrophysiological recordings. PBMC were also isolated from a separate cohort of HS, IBS-D and IBS-C (N = 4 each) and were labelled extracellularly with CD4, CD8 orCD14 and gut homing / CD45RO and intracellularly with TNF-a either unstimulated or following PMA/ionomycin stimulation. Cytokine content of unstimulated PBMC supernatants was determined using a13 plex bead based assay. Results: PBMC supernatants from IBS-D patients sensitised serosal afferents and this was significantly reduced following incubation with anti-TNFa, while IBS-C supernatant was without effect. TNF-a mimicked the sensitising effects, while IL-1b caused potent chemo-sensitive responses. PBMC supernatants from IBS-D patients had increased levels of TNF-a, IL-1b, IL-6, IL-10 and IFN-g that were not observed in IBS-C. The proportions of gut homing memory helper and cytotoxic T cells were increased in IBS-D and IBS-C, while TNF-a was increased in gut homing memory helper T cells in IBS-D but not IBS-C. Monocytes also had higher TNF-a levels in IBS-D. Conclusion: The sensitising effects of PBMC supernatants from IBS-D patients are predominantly mediated by TNF-a. More memory cells home to the GI tract in IBS-C and IBS-D. In IBS-D there is a shift toward aTH1 predominance, and gut homing memory T helper cells and monocytes contribute toward the increased TNF-a levels in IBS-D, while cytotoxic T cells do not.1: Hughes et. al. Gut 2009, 2: Liebregts et. al. Gastro-enterology 2007
Rights: © 2012 The Authors. Neurogastroenterology & Motility, Blackwell Publishing Ltd
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