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

Bennet, Sean; Palsson, Olafur S.; Barrow, David A.; Törnblom, Hans; Öhman, Lena; Simrén, Magnus; Tilburg, Miranda A.L. van

doi:10.1111/nmo.13378

Cited by 20 publications

(22 citation statements)

References 56 publications

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“…This approach identified a subset of IBS patients (33%), referred to as immuno‐active IBS, with evidence of increased immune activation in the colon descendens . These results are in line with previous studies showing increased immune activation in a subset of Swedish IBS patients based on multivariate analysis of serum levels and mucosal expression of a small set of 5 and 9 cytokines, respectively. To further evaluate the potential role of immune activation in IBS, we compared the clinical characteristics of immuno‐active vs immuno‐normal IBS patients.…”

Section: Discussionsupporting

confidence: 92%

“…To further evaluate the potential role of immune activation in IBS, we compared the clinical characteristics of immuno-active vs immuno-normal IBS patients. In line with two previous Swedish studies, 33,41 no differences in clinical symptoms could be identified between these two subgroups, suggesting no direct relationship between mucosal low-grade inflammation, assessed by gene expression analysis, and symptoms in IBS. However, previous clinical trials in IBS have reported clinical improvement with the mast cell stabilizer ketotifen 30 and the histamine 1 receptor antagonist ebastine 42 while a subgroup of IBS patients seems to respond to treatment with mesalazine.…”

Section: Discussionsupporting

confidence: 89%

“…In conclusion, our study demonstrates that the immune profile, defined by gene expression, in the rectum and colon descendens in IBS patients is largely similar to HV and cannot be used to discriminate patients from healthy controls. Of interest, and in line with previous studies, we identified a subgroup of IBS patients with increased immune activation in the colon descendens , especially influenced by IL1B, PTGS2, and MRGPRX2 . This subgroup of patients showed similar GI symptoms, somatization, anxiety, and depression scores than the rest of IBS patients, suggesting no direct relationship between mucosal low‐grade inflammation, defined by gene expression, and symptoms in IBS.…”

Section: Discussionsupporting

confidence: 85%

Section: Discussionsupporting

confidence: 72%

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Expression of immune‐related genes in rectum and colon descendens of Irritable Bowel Syndrome patients is unrelated to clinical symptoms

Aguilera‐Lizarraga

Florens

Brussel

et al. 2019

Neurogastroenterology Motil

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Background Mucosal immune activation has been postulated to play an important role in the pathogenesis of irritable bowel syndrome (IBS). However, data are conflicting and often based on small patient cohorts. Here, we aimed to evaluate the gene expression of a large set of immune‐related genes in mucosal biopsies from IBS patients and healthy volunteers (HV). Methods A total of 171 IBS patients and 127 HV were included in the study. Rectum biopsies were collected from a cohort of 70 HV and 77 IBS patients (Rome III) and colon descendens biopsies from another cohort of 57 HV and 94 IBS patients (Rome II). Gene expression was assessed using OpenArray technology, and validated questionnaires were used to evaluate clinical characteristics (GI symptoms, somatization, anxiety, and depression). Key Results A subset of IBS patients (33%) with increased immune activation in the colon descendens was identified using multivariate analysis and displayed increased gene expression of IL1B (3‐fold change), prostaglandin synthase PTGS2 (2.1‐fold change), and the G‐protein‐coupled receptor MRGPRX2 (10.7‐fold change). Clinical characteristics in this subgroup were however similar to the rest of the patient cohort. Analysis of rectal biopsies failed to identify such subgroup of “immuno‐active” IBS patients in the other patient cohort. Conclusion A subset of IBS patients reveals evidence of immune activation in the colon descendens, but not in the rectum; however, gene expression is unrelated to clinical symptoms. To what extent this subgroup might however respond to anti‐inflammatory therapy remains to be investigated.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 89%

Section: Discussionsupporting

confidence: 85%

Section: Discussionsupporting

confidence: 72%

See 2 more Smart Citations

Expression of immune‐related genes in rectum and colon descendens of Irritable Bowel Syndrome patients is unrelated to clinical symptoms

Aguilera‐Lizarraga

Florens

Brussel

et al. 2019

Neurogastroenterology Motil

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“…IBS is not an inflammatory disease as such, but growing evidence suggests that dysregulation in immune function is associated with at least a subgroup of IBS patients and could contribute to either etiology or symptoms (21,(120)(121)(122)(123)(124)(125).…”

Section: Immune Activation In Ibsmentioning

confidence: 99%

Exploring the Biopsychosocial Model in Irritable Bowel Syndrome : with emphasis on stress, comorbidities and fatigue

Norlin

2020

Linköping University Medical Dissertations

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Background Irritable bowel syndrome (IBS) is a common, chronic, relapsing, and sometimes disabling, symptom-based disorder of gut brain interactions. It has got a female predominance and occurs in all ages, with a slight decrease among elderly. The IBS symptoms can affect everyday work and social life in addition to an increased use of health care resources. Most IBS patients are diagnosed and helped in primary health care (PHC). For many patients, available treatment is insufficient. It is known that both extraintestinal symptoms such as fatigue, as well as comorbidities such as mood disorders, chronic pain syndromes, and insomnia contribute to the illness burden, often to a larger extent than the gastrointestinal symptoms as such. Eventhough the pathophysiology of IBS is not completely known, it is now conceptualized as a disorder of altered brain-gut interactions, where a biopsychosocial model helps in understanding the symptoms. Exposure to stress is thought to play an important role overall in the pathology of IBS, as well as immune activation at least in a subgroup of patients. This thesis aimed to gain deeper understanding of the biopsychosocial mechanisms of IBS and its associations with stress, comorbidities, and fatigue.

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Pentoxifylline, a nonselective phosphodiesterase inhibitor, in adjunctive therapy in patients with irritable bowel syndrome treated with mebeverine

El-Haggar

Hegazy

Bahaa

2022

Biomedicine & Pharmacotherapy

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

Abstract: 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.

Cited by 20 publications

References 56 publications

Expression of immune‐related genes in rectum and colon descendens of Irritable Bowel Syndrome patients is unrelated to clinical symptoms

Expression of immune‐related genes in rectum and colon descendens of Irritable Bowel Syndrome patients is unrelated to clinical symptoms

Exploring the Biopsychosocial Model in Irritable Bowel Syndrome : with emphasis on stress, comorbidities and fatigue

Pentoxifylline, a nonselective phosphodiesterase inhibitor, in adjunctive therapy in patients with irritable bowel syndrome treated with mebeverine

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