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Bernard P Leung, Naveed Sattar, Anne Crilly, Morag Prach, David W McCarey, Helen Payne, Rajan Madhok, Carol Campbell, J Alastair Gracie, Foo Y Liew, Iain B McInnes, A Novel Anti-Inflammatory Role for Simvastatin in Inflammatory Arthritis, The Journal of Immunology, Volume 170, Issue 3, February 2003, Pages 1524–1530, https://doi.org/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.