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

作者：McKernan D P^*; Gaszner G; Quigley E M; Cryan J F; Dinan T G

来源：Alimentary Pharmacology and Therapeutics, 2011, 33(9): 1045-1052.

DOI：10.1111/j.1365-2036.2011.04624.x

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 IL1 beta, IL6, IL8 and TNF alpha. Plasma was analysed for levels of inflammatory cytokines and cortisol.
Results
Toll-like receptor agonist-induced cytokine (IL1 beta, IL6, IL8 and TNF alpha) 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 TNF alpha release, TLR3-induced IL-8 release, TLR4-induced IL1 beta and TNF alpha release, TLR5-induced IL1 beta and TNF alpha 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.

• 出版日期2011-5-1