Altered levels of cytokines in patients with irritable bowel syndrome are not correlated with fatigue.

INTRODUCTION: A considerable number of patients with gastrointestinal complaints attributable to irritable bowel syndrome (IBS) have shown evidence of immune activation. Fatigue is also frequently reported by IBS patients and the condition is considered as a common comorbidity of IBS. Therefore, it is interesting to see whether these two conditions share the same pathophysiological mechanism. AIMS: To investigate the potential role of cytokine profiles in patients with IBS and the relationship between cytokine profiles and fatigue. MATERIALS AND METHODS: Thirty-eight patients with IBS (32 females, 6 males, age range 18-70 years) and 22 healthy individuals (control group) (17 females, 5 males, age range 24-42 years) were included. IBS was diagnosed according to Rome III criteria, and severity of IBS symptoms and fatigue were evaluated using the Irritable Bowel Syndrome-Severity Scoring System (IBS-SSS) and Fatigue Impact Scale (FIS), respectively. FIS scores of 25 or higher were defined as fatigue. Blood samples were also taken, and the Luminex® platform (Cytokine Human Ultrasensitive Magnetic 10-Plex Panel) was used for quantifying human cytokines' profile (granulocyte-macrophage colony-stimulating factor, interferon-γ, interleukin [IL]-1ß, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, and tumor necrosis factor [TNF]-α) in serum. RESULTS: The serum levels of IL-5, IL-6, IL-10, and TNF-α were significantly higher in patients with IBS compared to healthy controls (p=0.003, p=0.011, p=0.007, and p=0.02, respectively). Conversely, serum levels of cytokine IL-1ß were significantly higher in the control group (p=0.03). The findings were consistent when comparing nonatopic patients with controls. Fatigue was demonstrated in 84.2% of the IBS patients. Scores of IBS-SSS were not significantly correlated with FIS scores (r=0.2, p=0.19), and they were not significantly different in patients with FIS scores >25 compared to patients with FIS scores <25 (p=0.11). None of the cytokine levels were significantly different in IBS patients with FIS scores >25 compared to IBS patients with FIS scores <25. Moreover, the cytokine levels in participants did not vary significantly between patients with diarrhea, constipation, or mixed bowel habits in multiple comparisons of patients. CONCLUSIONS: The cytokines IL-5, IL-6, IL-10, and TNF-α may contribute to the development of IBS. However, serum levels of cytokines were not significantly different in IBS patients with fatigue compared with IBS patients without fatigue. Thus, the significance of cytokine levels may be less important than anticipated in search of common underlying mechanisms, and other factors should be explored in future studies.

Extra-intestinal symptoms in patients with irritable bowel syndrome: related to high total IgE levels and atopic sensitization?

Objective We have previously found that high levels of total IgE, but not atopic sensitization, was a significant predictor for functional gastrointestinal (GI) symptoms. In this study, we aimed to assess the prevalence of extra-intestinal symptoms in IBS patients, and explore their relation to total IgE levels and atopic sensitization. Materials and methods Seventy-one patients with functional GI complaints were included. Severity of GI symptoms, fatigue and musculoskeletal pain was evaluated using the following questionnaires: IBS-Severity Scoring System (IBS-SSS), Fatigue Impact Scale (FIS), FibroFatigue Scale (FFS), and Visual Analog Scales (VAS) for musculoskeletal pain. Levels of total IgE and specific IgE-antibodies were analyzed. Results Fatigue and musculoskeletal pain were demonstrated in 78.9 and 43.7% of the patients, respectively. IBS-SSS scores were significantly correlated with fatigue scores and musculoskeletal pain. Patients with fatigue and musculoskeletal pain had significantly higher IBS-SSS scores than patients without fatigue and musculoskeletal pain. Total IgE levels were significantly higher in IBS patients compared to a healthy control group from a previous study. However, neither total IgE nor atopic sensitization was significantly associated with extra-intestinal symptoms. Conclusions IBS, fatigue, and musculoskeletal pain were significantly associated. Total IgE levels were higher in IBS patients than healthy controls, but not related to intestinal or extra-intestinal symptom severity. Atopy was not associated with any of the co-morbidities. Thus, the clinical significance of high IgE levels in IBS remains unclear and further studies are warranted to explore a common underlying mechanism for the co-morbid triad of IBS, fatigue, and musculoskeletal pain.

Functional Gastrointestinal Symptoms Are Associated with Higher Serum Total IgE Levels, but Less Atopic Sensitization.

BACKGROUND: The relation of gastrointestinal (GI) complaints to IgE-mediated allergy is not well understood. Increased numbers of "IgE-armed" mast cells have been observed in duodenal mucosa of patients with functional GI complaints. AIMS: To explore whether total IgE and atopic sensitization were associated with functional GI complaints. METHODS: Levels of serum total and specific IgE and GI complaints were measured in 161 patients and in a general population sample of 478 persons. Standard inhalant allergens were measured in the patient group, and selected inhalant allergens in the general population. GI complaints were assessed by two standardized questionnaires. The associations between GI complaints and total IgE were analyzed in multiple regression models. RESULTS: GI complaints were positively associated with higher total IgE levels (all: b = 0.028, p = 0.012; patient group: b = 0.038, p = 0.072; general population: b = 0.038, p = 0.005), but negatively associated with atopic sensitization (all: b = -11.256, p = 0.181; patient group: b = -85.667, p < 0.001; general population: b = -14.394, p = 0.083). The relationship between total IgE and GI complaints was consistent among sensitized and non-sensitized persons, among men and women, and across age groups. CONCLUSION: Serum total IgE was positively associated with GI complaints, while atopic sensitization was inversely associated with GI complaints. This suggests that IgE-mediated immunology plays a role in the pathophysiology of functional GI complaints. The biological mechanisms reflected in higher total IgE levels, but less atopic sensitization, warrant further studies.