Cited by 324Inflammatory Bowel DiseaseCytokine Signaling Pathways and InteractionsPsoriasis: Treatment and Pathogenesis

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Involvement of IL–6 in the pathogenesis of inflammatory bowel disease and colon cancer

Atreya, Raja, Neurath, Markus F.·2005·Clinical Reviews in Allergy & Immunology

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Abstract

Inflammatory bowel disease (IBD), which consists of Crohn's disease and ulcerative colitis, is defined as a chronic inflammation of the gastrointestinal tract. The etiopathogenetic mechanisms underlying the development of IBD are still not completely understood, and the therapeutic strategies used thus far have been limited to mostly evidence-based principles. There is growing evidence that the pro-inflammatory cytokine interleukin (IL)-6 plays a crucial part in the uncontrolled intestinal inflammatory process, which is a main characteristic of IBD. There is elevated production of IL-6 and its soluble receptor (sIL-6R) by intestinal macrophages and CD4+T-cells. The increased formation of IL-6-sIL-6R complexes that interact with gp130 on the membrane of CD4+T-cells (trans-signaling) lead to an increased expression and nuclear translocation of STAT3, which causes the induction of anti-apoptotic genes, such as Bcl-xl. This leads to an augmented resistance of lamina propria T-cells to apoptosis. The ensuing T-cell expansion contributes to the perpetuation of chronic intestinal inflammation. This understanding concerning the predominant pathogenic role of an IL-6-dependent inflammatory cascade may lead to the development of new therapeutic strategies in the treatment of this disease. Recent studies have also suggested a potential role of IL-6-sIL-6R in the pathogenesis of colon cancer and, therefore, imply a possible novel therapeutic strategy targeting the sIL-6R and ensuing IL-6 trans-signaling.

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Authors: Atreya, R., & Neurath, M. F.
Affiliations: Johannes Gutenberg University Mainz (DE)
Corresponding author: Neurath, Markus F.
ORCID: Atreya, Raja
Neurath, Markus F.
Venue: Clinical Reviews in Allergy & Immunology
Publisher: Springer Science and Business Media LLC
Published: 2005
Volume: 28
Issue: 3
Pages: 187-196
ISSN: 1080-0549 (ISSN-L)
DOI: 10.1385/criai:28:3:187
OpenAlex: W2024255214
Cited by: 324
References: 57
Citations by year: 2026: 11 · 2025: 16 · 2024: 21 · 2023: 23 · 2022: 22 · 2021: 25 · 2020: 22 · 2019: 9 · 2018: 17 · 2017: 13 · 2016: 20 · 2015: 13 · 2014: 13 · 2013: 13 · 2012: 12
FWCI: 4.82
Type: journal article
Language: en
Open access: closed
Locations: Clinical Reviews in Allergy & Immunology (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Gastroenterology › Inflammatory Bowel Disease
Life Sciences › Immunology and Microbiology › Immunology › Cytokine Signaling Pathways and Interactions
Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
Keywords: interleukin-6, inflammatory bowel disease, Crohn's disease, ulcerative colitis, colon cancer, soluble IL-6 receptor, IL-6 trans-signaling, gp130, STAT3, Bcl-xL, T cell apoptosis, intestinal inflammation, CD4+ T cells, macrophages, anti-apoptotic genes
MeSH terms: Animals, Humans, Colorectal Neoplasms, Inflammatory Bowel Diseases, Interleukin-6

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Involvement of IL–6 in the pathogenesis of inflammatory bowel disease and colon cancer

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