title: Altered peripheral toll-like receptor responses in the irritable bowel syndrome.
abstract: 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.
  
  
  OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors: Alimentary Pharmabiotic Centre, University College Cork, Ireland. d.mckernan@ucc.ie
authors: D P
authors: DP
authors: McKernan
authors: G
authors: G
authors: Gaszner
authors: E M
authors: EM
authors: Quigley
authors: J F
authors: JF
authors: Cryan
authors: T G
authors: TG
authors: Dinan
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism*; D007113:Immunity, Innate / Q000502:physiology; D007378:Interleukins / Q000378:metabolism*; D043183:Irritable Bowel Syndrome / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology; D008297:Male; D054892:Metagenome; D008875:Middle Aged; D051193:Toll-Like Receptors / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D007378:Interleukins; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha; D006854:Hydrocortisone