Altered peripheral toll-like receptor responses in the irritable bowel syndrome

Aliment Pharmacol Ther. 2011 May;33(9):1045-52. doi: 10.1111/j.1365-2036.2011.04624.x. Epub 2011 Mar 9.

Altered peripheral toll-like receptor responses in the irritable bowel syndrome.

McKernan DP, Gaszner G, Quigley EM, Cryan JF, Dinan TG.

Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland. Department of Psychiatry, University College Cork, Cork, Ireland. School of Pharmacy, University College Cork, Cork, Ireland. Department of Pharmacology & Therapeutics, University College Cork, Cork, Ireland.

Background: Irritable bowel syndrome (IBS) is a stress-related disorder with disturbed brain-gut communication, gastrointestinal homeostasis and, based on recent evidence, low grade inflammation and an altered microbiota. The immune system is a critical regulator of the brain-gut axis. Toll-like receptors (TLRs) are pattern recognition molecules regulating innate immunity. Aim To characterise toll-like receptor activity in IBS.

Methods: Thirty IBS patients and 30 healthy controls (HC) were recruited. Venous blood was collected, and cultured with a panel of toll-like receptor agonists for 24 h. Cell supernatants were analysed using a multiplex ELISA approach to measure IL1β, IL6, IL8 and TNFα. Plasma was analysed for levels of inflammatory cytokines and cortisol.

Results: Toll-like receptor agonist-induced cytokine (IL1β, IL6, IL8 and TNFα) release was markedly enhanced in stimulated whole blood from IBS (n = 30) patients compared with healthy controls (n = 30). An exaggerated response to the TLR8 agonist for all cytokines investigated was seen in IBS patients. In addition, enhanced TLR2-induced TNFα release, TLR3-induced IL-8 release, TLR4-induced IL1β and TNFα release, TLR5-induced IL1β and TNFα release and TLR7-induced IL-8 release were also observed in IBS patients. No differences in TLR1, TLR6 or TLR9 activity were detected. In addition, plasma levels of cortisol, IL-6 and IL-8 were significantly increased in IBS patients.

Conclusion: Taken together, these data demonstrate elevated cytokine levels and toll-like receptor activity in the periphery of patients with the irritable bowel syndrome, indicating some immune dysregulation in these patients.

PMID: 21453321 [PubMed - in process]

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