Systemic cytokines are elevated in a subset of patients with irritable bowel syndrome but largely unrelated to symptom characteristics

Background Serum levels of pro‐inflammatory cytokines tend to be increased in irritable bowel syndrome (IBS) patients, or subgroups thereof. Still, the link between cytokine levels and IBS symptoms is unclear. We aim to determine systemic cytokine levels in IBS patients and healthy subjects (HS), confirm the presence of a subset of patients with an increased immune activity and to establish if cytokines are linked to IBS symptoms and pathophysiological factors. Methods Serum levels of interleukin (IL)‐1β, IL‐6, IL‐8, tumor necrosis factor (TNF), and IL‐10 were measured. All subjects reported IBS symptoms using validated questionnaires and underwent colonic sensorimotor testing. Multivariate supervised orthogonal partial least squares‐discriminant analysis (OPLS‐DA) and unsupervised principal component analysis (PCA) and hierarchical cluster analysis (HCA) were implemented. Key Results Irritable bowel syndrome patients (n = 246) had higher serum levels of IL‐1β, IL‐6, IL‐8, TNF, and IL‐10 compared to HS (n = 21); however, serum cytokine profiles could not discriminate patients from HS. Moreover, cytokine levels were not correlated with symptoms among patients. Supervised OPLS‐DA identified 104 patients (40% of patients) and unsupervised HCA analysis identified 49 patients (20%) with an increased immune activity indicated by elevated levels of serum cytokines compared to HS and the other patients. However, irrespective of how patients with increased immune activity were identified they were symptomatically similar to patients with no indication of increased immune activity. Conclusions & Inferences Serum cytokines are elevated in IBS patients compared to HS. Immune activation characterizes a subset of patients, but modest associations between cytokine profile and symptoms suggest immune activity does not directly influence symptoms in IBS. Using 2 independent statistical methods, we have again identified in a new cohort a subset of IBS patients with an increased immune activity compared to healthy subjects and IBS patients with an immune activity level comparable to the healthy subjects. While there were no strong association with immune activity and IBS symptoms, the cause for the increased immune activity in these patients requires elucidation and may still be relevant in the pathogenesis of their IBS.