A Novel Anti-Inflammatory Role for Simvastatin in Inflammatory Arthritis
Bernard P. Leung,Naveed Sattar,Anne Crilly,Morag Prach,D McCarey,Helen Payne,Rajan Madhok,Carol Campbell,J. Alastair Gracie,Foo Y. Liew,Iain B. McInnes +10 more
TLDR
It is reported 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.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.read more
Citations
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Cytokines in atherosclerosis: pathogenic and regulatory pathways.
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Explaining How “High-Grade” Systemic Inflammation Accelerates Vascular Risk in Rheumatoid Arthritis
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Trial of Atorvastatin in Rheumatoid Arthritis (TARA): double-blind, randomised placebo-controlled trial
D McCarey,Iain B. McInnes,Rajan Madhok,R Hampson,Olga Scherbakova,Ian Ford,Hilary A Capell,Naveed Sattar +7 more
TL;DR: These data show that statins can mediate modest but clinically apparent anti-inflammatory effects with modification of vascular risk factors in the context of high-grade autoimmune inflammation.
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Therapeutic Strategies for Rheumatoid Arthritis
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