Irritable bowel syndrome (IBS) is a functional disorder that is associated with a number of extra-intestinal co-morbidities and a pro-inflammatory profile. This study was designed to examine the cytokine profile among a group of IBS patients with the extra-intestinal co-morbidities fibromyalgia, premenstrual dysmorphic disorder, and chronic fatigue syndrome. In all, 100 female IBS patients with these co-morbidities, 21 IBS subjects without co-morbidity (“pure” IBS; Rome II), and 54 age-matched female controls took part in the study. Blood was drawn for measurement of the plasma cytokines interleukin (IL)-1β, IL-6, IL-8, IL-10, IL-12p70, IL-13, tumor necrosis factor (TNF)α, and interferon γ. The presence of the selected extra-intestinal manifestations was assessed using standard international criteria. Patients with IBS have increased plasma levels of IL-6 and IL-8; those with these extra-intestinal co-morbidities were found to have, in addition, increased levels of IL-1β and TNFα. No associations were evident between cytokine profiles and the nature of the co-morbidity or number of extra-intestinal co-morbidities present. Although IBS is characterized by a pro-inflammatory profile featuring the pro-inflammatory cytokines IL-6 and IL-8, IBS patients with certain extra-intestinal co-morbid conditions are distinguished by additional elevations in IL-1β and TNFα.

Aliment Pharmacol Ther 2011; 33: 1045–1052 Summary 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.