Cited by 174Gastrointestinal motility and disordersInflammatory Bowel DiseaseGut microbiota and health

Mucosal cytokine imbalance in irritable bowel syndrome

Macsharry, John, O'Mahony, Liam, Fanning, Aine, Bairead, Emer, Sherlock, Graham, Tiesman, Jay, Fulmer, Andy, Kiely, Barry +3 more·2008·Scandinavian Journal of Gastroenterology

Abstract

OBJECTIVE: To systematically examine mucosal biopsies for differences in cytokine gene expression and protein secretion. MATERIAL AND METHODS: The study included 59 females with irritable bowel syndrome (IBS) and 39, otherwise healthy, female volunteers presenting for colonoscopy. Colonic biopsies from subsets were studied by microarray analysis (IBS, n=9; controls, n=8), quantitative reverse transcription-polymerase chain reaction (qRT-PCR) (IBS, n=22; controls, n=21), and ex vivo biopsy culture (IBS, n=28, controls, n=10). Biopsies from patients with active colitis were used as inflammatory disease controls. RESULTS: While gene array analysis revealed extensive overlapping between controls and IBS patients, reduced expression of genes linked to chemokine function was evident among the IBS patients alone. Differential expression was confirmed by qRT-PCR or ex vivo biopsy culture for 5 out of 6 selected genes. Reduced secretion of chemokines (IL-8, CXCL-9 and MCP-1) but not pro-inflammatory cytokines (TNF-alpha, IL-6 and IL-1beta) was established on the basis of the ex vivo biopsy cultures. These findings were in marked contrast to the IBD patients who demonstrated increased production of both chemokines and pro-inflammatory cytokines. CONCLUSIONS: Despite the expected heterogeneity of the disorder, differences in mucosal chemokine signalling were evident in this cross-sectional study of IBS patients at the level of both gene expression and protein secretion, with IBS patients demonstrating a consistent deficit in the expression and secretion of chemokines known to play a critical role in mucosal defence.

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Registry

Crossref · 10.1080/00365520802276127

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  • Ex vivo examination of cytokine secretion by the colon failed to show elevation of proinflammatory cytokines or chemokines in patients with IBS compared with controls.

    “Ex vivo examination of cytokine secretion by the colon failed to show elevation of proinflammatory cytokines or chemokines in patients with IBS compared with controls (102).”
  • In the Macsharry study, a decreased level of mRNA encoding the anti-inflammatory IL-10 gene was observed, as well as an altered IL-10:IL-12 ratio in colonic biopsies from patients with IBS compared with controls.

    “However, in this study a decreased level of mRNA encoding the anti-inflammatory IL-10 gene was observed, as well as an altered IL-10:IL-12 ratio in colonic biopsies from patients with IBS compared with controls, supporting the hypothesis that patients with IBS have a dysfunctional immunological response in the mucosa.”
  • A study by Macsharry and colleagues found reduced levels of IL-1β mRNA in colonic biopsies from patients with IBS.

    “In contrast, a study by Macsharry and colleagues (102) found reduced levels of IL-1β mRNA in colonic biopsies from patients with IBS.”

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Authors
Macsharry, J., O'Mahony, L., Fanning, A., Bairead, E., Sherlock, G., Tiesman, J., Fulmer, A., Kiely, B., Dinan, T. G., Shanahan, F., & Quigley, E. M. M.
Affiliations
  • Alimentary Health (Ireland) (IE)
  • University College Cork (IE)
  • Procter & Gamble (United States) (US)
Corresponding author
Quigley, Eamonn M. M.
Venue
Scandinavian Journal of Gastroenterology
Published
2008-01
Volume
43
Issue
12
Pages
1467-1476
ISSN
  • 0036-5521 (ISSN-L)
  • 1502-7708
OpenAlex
W2116909437
Cited by
174
References
40
Citations by year
2026: 2 · 2025: 2 · 2024: 8 · 2023: 6 · 2022: 2 · 2021: 9 · 2020: 10 · 2019: 5 · 2018: 6 · 2017: 13 · 2016: 11 · 2015: 10 · 2014: 15 · 2013: 13 · 2012: 20
FWCI
13.81
Type
journal article
Language
en
Open access
closed
Locations
  • Scandinavian Journal of Gastroenterology (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Inflammatory Bowel Disease
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
Keywords
irritable bowel syndrome, colonic mucosa, cytokine gene expression, chemokines, interleukin-8, CXCL9, MCP-1, inflammatory cytokines, mucosal protection, inflammatory bowel disease, colonoscopic biopsy
MeSH terms
Adolescent, Adult, Aged, Colonoscopy, Female, Humans, Intestinal Mucosa, Middle Aged, Tumor Necrosis Factor-alpha, Interleukin-6, Gene Expression, Cytokines, Interleukin-8, Chemokine CCL2, Reverse Transcriptase Polymerase Chain Reaction, Irritable Bowel Syndrome, Interleukin-1beta, Chemokine CXCL9

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