Cited by 434Rheumatoid Arthritis Research and TherapiesNatural Compounds in Disease TreatmentInflammatory mediators and NSAID effects

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A novel anti-inflammatory role for simvastatin in inflammatory arthritis.

Leung, Bernard P, Sattar, Naveed, Crilly, Anne, Prach, Morag, McCarey, David W, Payne, Helen, Madhok, Rajan, Campbell, Carol, Gracie, J Alastair, Liew, Foo Y, McInnes, Iain B·2003·The Journal of Immunology

DOI 10.4049/jimmunol.170.3.1524

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Abstract

3-Hydroxy-3-methylglutaryl-CoA reductase inhibitors (statins) exert favorable effects on lipoprotein metabolism, but may also possess anti-inflammatory properties. Therefore, we explored the activities of simvastatin, a lipophilic statin, in a Th1-driven model of murine inflammatory arthritis. We report in this study that simvastatin markedly inhibited not only developing but also clinically evident collagen-induced arthritis in doses that were unable to significantly alter cholesterol concentrations in vivo. Ex vivo analysis demonstrated significant suppression of collagen-specific Th1 humoral and cellular immune responses. Moreover, simvastatin reduced anti-CD3/anti-CD28 proliferation and IFN-γ release from mononuclear cells derived from peripheral blood and synovial fluid. Proinflammatory cytokine production in vitro by T cell contact-activated macrophages was suppressed by simvastatin, suggesting that such observations have direct clinical relevance. These data clearly illustrate the therapeutic potential of statin-sensitive pathways in inflammatory arthritis.

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Authors: Leung, B. P., Sattar, N., Crilly, A., Prach, M., McCarey, D. W., Payne, H., Madhok, R., Campbell, C., Gracie, J. A., Liew, F. Y., & McInnes, I. B.
Affiliations: University of Glasgow (GB)
Glasgow Royal Infirmary (GB)
Corresponding author: Campbell, Carol
ORCID: Leung, Bernard P
Sattar, Naveed
Crilly, Anne
Payne, Helen
Madhok, Rajan
Gracie, J Alastair
McInnes, Iain B
Venue: The Journal of Immunology
Publisher: Oxford University Press (OUP)
Published: 2003-02-01
Volume: 170
Issue: 3
Pages: 1524-1530
ISSN: 0022-1767 (ISSN-L)
1550-6606
DOI: 10.4049/jimmunol.170.3.1524
OpenAlex: W2155440953
Cited by: 434
References: 38
Citations by year: 2026: 4 · 2025: 3 · 2024: 3 · 2023: 6 · 2022: 14 · 2021: 12 · 2020: 7 · 2019: 8 · 2018: 11 · 2017: 10 · 2016: 12 · 2015: 17 · 2014: 17 · 2013: 24 · 2012: 24
FWCI: 25.31
Type: journal article
Language: en
Open access: closed
Licence: academic.oup.com/pages/standard-publication-reuse-rights (vor)
Locations: The Journal of Immunology (publishedVersion)
PubMed (publishedVersion)
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 › Pharmacology (medical) › Inflammatory mediators and NSAID effects
Keywords: simvastatin, statins, inflammatory arthritis, collagen-induced arthritis, Th1 response, anti-inflammatory activity, interferon-gamma, inflammatory cytokines, T cell activation, macrophages, synovial fluid, cholesterol-independent effects
MeSH terms: Animals, Anti-Inflammatory Agents, Non-Steroidal, Arthritis, Experimental, Arthritis, Rheumatoid, Cells, Cultured, Collagen, Disease Models, Animal, Humans, Immune Sera, Immunosuppressive Agents, Injections, Intraperitoneal, Macrophages, Male, Mice, Inbred CBA, CD3 Complex, CD28 Antigens, Th1 Cells, Coculture Techniques, Epitopes, T-Lymphocyte, Simvastatin, Mice

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A novel anti-inflammatory role for simvastatin in inflammatory arthritis.

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