Altered Peripheral Toll-like Receptor Responses in Irritable Bowel Syndrome

Declan Patrick Mckernan (1) , Gabor Gaszner , Eamonn Quigley (2) , John F Cryan (3) , Ted G Dinan (3)

1 APC - Alimentary Pharmabiotic Centre
2 Cork University Hospital
3 Alimentary Pharmabiotic Centre

Background & Aims: 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. The aim of this study was to characterize TLR activity in IBS. Methods: Thirty IBS patients and 30 healthy controls (HC) were recruited. Venous blood was collected, and cultured with a panel of TLR agonists for 24 hours. 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: TLR 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 TLR activity in the periphery of IBS patients indicating some immune dysregulation in IBS patients.

Mots clés: Medicine

Declan Patrick Mckernan, Gabor Gaszner, Eamonn Quigley, John F Cryan, Ted G Dinan. Altered Peripheral Toll-like Receptor Responses in Irritable Bowel Syndrome. Alimentary Pharmacology and Therapeutics, 2011, 33 (9), pp.1045. ⟨10.1111/j.1365-2036.2011.04624.x⟩. ⟨hal-00620892⟩