IL-6 is required for the development of Th1 cell-mediated murine colitis
Open accessAbstract
Proinflammatory cytokines have been demonstrated to play a crucial role in the pathogenesis of Crohn’s disease. Among those cytokines, strong expression of IL-6 has been repeatedly demonstrated. To examine the role for IL-6 in the pathogenesis of Crohn’s disease, we introduced anti-IL-6R mAb to a murine model of colitis. Colitis was induced in C.B-17-scid mice transferred with CD45RBhigh CD4+ T cells from BALB/c mice. Anti-IL-6R mAb or rat IgG was administered weekly after T cell transfer. ICAM-1 and VCAM-1 expression were analyzed by immunohistochemistry. Colonic cytokine expression was determined by RT-PCR. Mice treated with mAb showed normal growth, whereas controls lost weight. The average colitis score was 0.64 for mAb-treated mice and 1.80 for controls. T cell expansion in treated mice was less remarkable than in the controls. Colonic ICAM-1 and VCAM-1 expression were markedly suppressed by mAb. IFN-γ, TNF-α, and IL-1β mRNA were reduced by the treatment. The results presented here show a crucial role for IL-6 in the pathogenesis of murine colitis and suggest a therapeutic potential of anti-IL-6R mAb for treatment of human Crohn’s disease.
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IL-6 production may enhance mucosal inflammation via T cell activation.
“Moreover, IL-6 production may enhance mucosal inflammation via T cell activation,6,35,36 providing a link between inflammation and tumour growth.”
From PU.1-driven Th9 Cells Promote Colorectal Cancer in Experimental Colitis Models Through Il-6 Effects in Intestinal Epithelial Cells (2022) · cites this paper as [36]
Genetic deletion of STAT3 in innate immune cells, such as myeloid cells (neutrophils and macrophages), and enterocytes results in chronic colitis.
“In contrast, genetic deletion of STAT3 in innate immune cells, such as myeloid cells (neutrophils and macrophages), and enterocytes resulted in chronic colitis (Takeda et al., 1999; Atreya et al., 2000; Yamamoto et al., 2000; Suzuki et al., 2001; Pickert et al., 2009).”
From Targeting Janus Kinases and Signal Transducer and Activator of Transcription 3 To Treat Inflammation, Fibrosis, and Cancer: Rationale, Progress, and Caution (2020) · cites this paper as Yamamoto et al., 2000
The ‘Anti-IL-6R mAb treatment prevents the development of colitis’ section reports antibody treatment in mice given CD4+ T cells, not genetic deletion of STAT3. Searches for STAT3 deletion in myeloid cells and enterocytes found no passage addressing whether those deletions cause chronic colitis; the paper’s different intervention is not a contradiction. (LLM, conf=0.76)
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- Ohshima, S., Y. Saeki, T. Mima, M. Sasai, K. Nishioka, S. Nomura, M. Kopf, Y. Katada, T. Tanaka, M. Suemura, and T. Kishimoto. 1998. Interleukin 6 plays a key role in the development of antigen-induced arthritis. Proc. Natl. Acad. Sci. USA 95:8222.
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“In contrast, genetic deletion of STAT3 in innate immune cells, such as myeloid cells (neutrophils and macrophages), and enterocytes resulted in chronic colitis (Takeda et al., 1999; Atreya et al., 2000; Yamamoto et al., 2000; Suzuki et al., 2001; Pickert et al., 2009).”
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- Authors
- Yamamoto, M., Yoshizaki, K., Kishimoto, T., & Ito, H.
- Affiliations
- The University of Osaka (JP)
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2000-05-01
- Volume
- 164
- Issue
- 9
- Pages
- 4878-4882
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W1920075805
- Cited by
- 411
- References
- 0
- Citations by year
- 2026: 4 · 2025: 1 · 2024: 10 · 2023: 11 · 2022: 17 · 2021: 11 · 2020: 17 · 2019: 16 · 2018: 15 · 2017: 16 · 2016: 19 · 2015: 21 · 2014: 19 · 2013: 16 · 2012: 8
- FWCI
- 10.92
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Chugai Pharmaceutical (MR16-1)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Inflammatory Bowel Disease
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Health Sciences › Medicine › Rheumatology › Rheumatoid Arthritis Research and Therapies
- Keywords
- interleukin-6, IL-6 receptor, Crohn's disease, murine colitis model, ICAM-1, VCAM-1, inflammatory cytokines, interferon-gamma, TNF-α, IL-1β
- MeSH terms
- Interleukin-6 Inhibitors, Animals, Antibodies, Monoclonal, Cell Differentiation, Colitis, Colon, Immunity, Cellular, Interferon-gamma, Mice, Inbred BALB C, CD4-Positive T-Lymphocytes, Interleukin-6, Cytokines, Mice, SCID, Th1 Cells, Intercellular Adhesion Molecule-1, Vascular Cell Adhesion Molecule-1, Antibodies, Blocking, Wasting Syndrome, Receptors, Interleukin-6, Mice
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