A novel anti-inflammatory role for simvastatin in inflammatory arthritis.
J Immunol
; 170(3): 1524-30, 2003 Feb 01.
Article
em En
| MEDLINE
| ID: mdl-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-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.
Buscar no Google
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Artrite Experimental
/
Anti-Inflamatórios não Esteroides
/
Sinvastatina
Limite:
Animals
/
Humans
/
Male
Idioma:
En
Revista:
J Immunol
Ano de publicação:
2003
Tipo de documento:
Article
País de afiliação:
Reino Unido