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

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. To characterise toll-like receptor activity in IBS. 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. 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. 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.