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Cited by 604Rheumatoid Arthritis Research and TherapiesNatural Compounds in Disease TreatmentCytokine Signaling Pathways and Interactions

Interleukin 6 is required for the development of collagen-induced arthritis

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Alonzi, Tonino, Fattori, Elena, Lazzaro, Domenico, Costa, Patrizia, Probert, Lesley, Kollias, George, De Benedetti, Fabrizio, Poli, Valeria +1 more·1998·The Journal of Experimental Medicine
DOI 10.1084/jem.187.4.461PMC PMC2212160
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Abstract

Interleukin-6 (IL-6) is overproduced in the joints of patients with rheumatoid arthritis (RA) and, based on its multiple stimulatory effects on cells of the immune system and on vascular endothelia, osteoclasts, and synovial fibroblasts, is believed to participate in the development and clinical manifestations of this disease. In this study we have analysed the effect of ablating cytokine production in two mouse models of arthritis: collagen-induced arthritis (CIA) in DBA/1J mice and the inflammatory polyarthritis of tumor necrosis factor α (TNF-α) transgenic mice. IL-6 was ablated by intercrossing an IL-6 null mutation into both arthritis-susceptible genetic backgrounds and disease development was monitored by measuring clinical, histological, and biochemical parameters. Two opposite responses were observed; while arthritis in TNF-α transgenic mice was not affected by inactivation of the IL-6 gene, DBA/1J, IL-6−/− mice were completely protected from CIA, accompanied by a reduced antibody response to type II collagen and the absence of inflammatory cells and tissue damage in knee joints. These results are discussed in the light of the present knowledge of cytokine networks in chronic inflammatory disorders and suggest that IL-6 receptor antagonists might be beneficial for the treatment of RA.

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  • IL-6 is required for type II collagen-induced arthritis, antigen-induced arthritis, experimental autoimmune encephalomyelitis, pristane-induced autoantibody production and plasmacytoma.

    “By utilizing IL-6-deficient mice, it was shown that IL-6 is required for type II collagen-induced arthritis (249), antigen-induced arthritis (AIA) (250), EAE (251, 252), pristane-induced autoantibody production (253) and plasmacytoma (254)”

    From IL-6 in inflammation, autoimmunity and cancer (2021) · cites this paper as [249]

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Authors
Alonzi, T., Fattori, E., Lazzaro, D., Costa, P., Probert, L., Kollias, G., De Benedetti, F., Poli, V., & Ciliberto, G.
Affiliations
  • University of Pavia (IT)
  • From the *Istituto Ricerche di Biologia Molecolare P.  Angeletti, 00040 Pomezia, Rome, Italy; the ‡Department of Molecular Genetics, Hellenic Pasteur Institute, 115 21 Athens, Greece; and the §Clinica Pediatrica, Universita' degli Studi di Pavia, Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo, 27100 Pavia, Italy
ORCID
Venue
The Journal of Experimental Medicine
Publisher
Rockefeller University Press
Published
1998-02-16
Volume
187
Issue
4
Pages
461-468
ISSN
  • 0022-1007 (ISSN-L)
  • 1540-9538
DOI
10.1084/jem.187.4.461
PMC
PMC2212160
OpenAlex
W2005260135
Cited by
604
References
1
Citations by year
2026: 6 · 2025: 6 · 2024: 4 · 2023: 10 · 2022: 14 · 2021: 21 · 2020: 14 · 2019: 16 · 2018: 18 · 2017: 17 · 2016: 13 · 2015: 18 · 2014: 22 · 2013: 32 · 2012: 28
FWCI
13.44
Type
journal article
Language
en
Open access
Licence
cc-by-nc-sa
Locations
  • The Journal of Experimental Medicine (publishedVersion)
  • PubMed Central (publishedVersion, cc-by-nc-sa)
  • PubMed (publishedVersion)
  • Institutional Research Information System University of Turin (University of Turin) (submittedVersion)
Topics
  • Health Sciences › Medicine › Rheumatology › Rheumatoid Arthritis Research and Therapies
  • Health Sciences › Medicine › Complementary and alternative medicine › Natural Compounds in Disease Treatment
  • Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
Keywords
interleukin-6, collagen-induced arthritis, rheumatoid arthritis, DBA/1J mice, TNF-alpha transgenic mice, arthritis susceptibility, cytokine network, IL-6 receptor inhibitor, synovitis
MeSH terms
Animals, Antibodies, Monoclonal, Arthritis, Collagen, Drug Interactions, Male, Mice, Inbred DBA, Mice, Transgenic, Tumor Necrosis Factor-alpha, Interleukin-6, Mice, Knockout, Mice

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