A novel anti-inflammatory role for simvastatin in inflammatory arthritis

Campbell, C. et al. (2003) A novel anti-inflammatory role for simvastatin in inflammatory arthritis. Journal of Immunology, 170, pp. 1524-1530. (doi: 10.4049/jimmunol.170.3.1524) (PMID:12538717)

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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: McInnes, Professor Iain and Liew, Prof Foo and Leung, Dr Bernard and Sattar, Professor Naveed
• Authors: Campbell, C., Crilly, A., Gracie, J., Leung, B., Liew, F., Madhok, R., McCarey, D., McInnes, I., Payne, H., Prach, M., and Sattar, N.
• College/School: College of Medical Veterinary and Life Sciences; College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health; College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: Journal of Immunology
• ISSN: 0022-1767