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.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“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
Citations
Cites
Atherosclerosis--an inflammatory disease
Ross, R. (1999) · New England Journal of Medicine · doi:10.1056/nejm199901143400207 · Cited by 21,725
Arnett, F. C., Edworthy, S. M., Bloch, D. A., McShane, D. J., Fries, J. F., Cooper, N. S., Healey, L. A., Kaplan, S. R., Liang, M. H., Luthra, H. S., et al. (1988) · Arthritis & Rheumatism · doi:10.1002/art.1780310302 · Cited by 19,753
OLSSON, A. G., McMurray, J. J. V., Thorgeirsson, G., Spaulding, C. M., Slattery, J., Pyörälà, K., Færgeman, O., Wright, R. S., Berg, K. M., Wilhelmsen, L., et al. (1994) · The Lancet · Cited by 8,467
Prevention of Coronary Heart Disease with Pravastatin in Men with Hypercholesterolemia
Shepherd, J., Cobbe, S. M., Ford, I., Isles, C. G., Lorimer, A. R., Macfarlane, P. W., McKillop, J. H., & Packard, C. J. (1995) · New England Journal of Medicine · doi:10.1056/nejm199511163332001 · Cited by 7,449
Pedersen, T. R. (2004) · Atherosclerosis Supplements · doi:10.1016/j.atherosclerosissup.2004.08.027 · Cited by 3,098
ROLE OF CYTOKINES IN RHEUMATOID ARTHRITIS
Feldmann, M., Brennan, F. M., & Maini, R. N. (1996) · Annual Review of Immunology · doi:10.1146/annurev.immunol.14.1.397 · Cited by 2,507
Stimulation of Bone Formation in Vitro and in Rodents by Statins
Mundy, G. R., Garrett, R., Harris, S., Chan, J., Chen, D., Rossini, G., Boyce, B. F., Zhao, M., & Gutierrez, G. (1999) · Science · doi:10.1126/science.286.5446.1946 · Cited by 1,776
Statins and the risk of dementia
Jick, H., Zornberg, G. L., Jick, S. S., Seshadri, S. S., & Drachman, D. (2000) · The Lancet · doi:10.1016/s0140-6736(00)03155-x · Cited by 1,764
Tuomilehto, J., Vidgrén, G., Toivanen, L., Tuomilehto‐Wolf, E., Kohtamäki, K., Stengård, J., Zimmet, P., Mackay, I. R., Rowley, M. J., & Koskela, P. U. (1994) · The Lancet · doi:10.1016/s0140-6736(94)92521-6 · Cited by 1,691
Research works printed but not linked: 34
- 1995, N. Engl. J. Med., 1301
- 1994, Lancet, 1383
- 1999, N. Engl. J. Med., 115
- 2001, Ann. Endocrinol., 101
- 2000, Nat. Med., 1399
- 2001, J. Clin. Invest., 1423
- 2001, Nat. Med., 687
- 1997, Curr. Opin. Immunol., 872
- 1998, J. Clin. Invest., 1717
- 2001, Circulation, 197
- 1996, Annu. Rev. Immunol., 397
- 1992, Scand. J. Immunol., 603
- 1995, Ann. Rheum. Dis., 654
- 1996, Arthritis Rheum., 1961
- 1999, Arthritis Rheum., 963
- 1994, J. Biol. Chem., 22027
- 1997, Nat. Med., 189
- 1997, Arthritis Rheum., 249
- 1999, Science, 1946
- 2001, J. Clin. Invest., 391
- 2001, Circ. Res., 415
- 1980, J. Clin. Invest., 1094
- 1988, Arthritis Rheum., 315
- 2000, J. Immunol., 6495
- 2001, Arterioscler. Thromb. Vasc. Biol., 115
- 2001, Rheum Dis. Clin. North Am., 373
- 2001, Annu. Rev. Immunol., 163
- 2000, Arthritis Res., 374
- 1999, Lancet, 983
- 2001, Arterioscler. Thromb. Vasc. Biol., 3
- 2001, Blood, 2381
- 1995, N. Engl. J. Med., 621
- 2001, Circulation, 357
- 2000, Lancet, 1627
Cited by
Sorted by citations
Cytokines in Atherosclerosis: Pathogenic and Regulatory Pathways
Tedgui, A., & Mallat, Z. (2006) · Physiological Reviews · doi:10.1152/physrev.00024.2005 · Cited by 1,751
Apoptotic cell clearance: basic biology and therapeutic potential
Poon, I. K. H., Lucas, C. D., Rossi, A. G., & Ravichandran, K. S. (2014) · Nature Reviews Immunology · doi:10.1038/nri3607 · Cited by 1,223
Explaining How “High-Grade” Systemic Inflammation Accelerates Vascular Risk in Rheumatoid Arthritis
Sattar, N. A., McCarey, D. W., Capell, H. A., & McInnes, I. B. (2003) · Circulation · doi:10.1161/01.cir.0000099844.31524.05 · Cited by 932
Self-citationMcCarey, D. W., McInnes, I. B., Madhok, R., Hampson, R., Scherbakova, O., Ford, I., Capell, H. A., & Sattar, N. A. (2004) · The Lancet · doi:10.1016/s0140-6736(04)16449-0 · Cited by 814
Self-citationStatin therapy and autoimmune disease: from protein prenylation to immunomodulation
Greenwood, J., Steinman, L., & Zamvil, S. S. (2006) · Nature reviews. Immunology · doi:10.1038/nri1839 · Cited by 696
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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review