1. Academic Validation
  2. A novel anti-inflammatory role for simvastatin in inflammatory arthritis

A novel anti-inflammatory role for simvastatin in inflammatory arthritis

  • J Immunol. 2003 Feb 1;170(3):1524-30. doi: 10.4049/jimmunol.170.3.1524.
Bernard P Leung 1 Naveed Sattar Anne Crilly Morag Prach David W McCarey Helen Payne Rajan Madhok Carol Campbell J Alastair Gracie Foo Y Liew Iain B McInnes
Affiliations

Affiliation

  • 1 Department of Immunology, Glasgow Royal Infirmary, University of Glasgow, Glasgow, United Kingdom.
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-gamma 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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