The DOI matches its Crossref record; 39 of the 39 references it cites were found in a registry or an index.
A novel anti-inflammatory role for simvastatin in inflammatory arthritis.
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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“Multiple reports indicate that statins have anti-inflammatory and immunomodulatory properties affecting both Th1 and Th2 immune responses (Leung et al., 2003; McKay et al., 2004; Palaniswamy et al., 2010).”
From Atorvastatin Reduces the Survival of Candida albicans-Infected BALB/c Mice (2015) · cites this paper as Leung et al., 2003
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Metadata
- 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
- 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
- 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
- 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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