Influence of simvastatin on the production of pro-inflammatory cytokines and nitric oxide by activated human chondrocytes

Clinical and Experimental Rheumatology

W.J. Stevens¹  E.J. Dombrecht¹  J.F. Van Offel¹  V. Seynhaeve¹  C.H. Bridts¹  L.S. De Clerck¹  A.J. Schuerwegh¹  D.G. Ebo¹ 

关键词: Rheumatoid arthritis;    chondrocytes;    statins;    interleukin-6;    interleukin-8;    nitric oxide;   

DOI  :  

学科分类：医学（综合）

来源: Pacini Editore SpA

【 摘 要 】

OBJECTIVES:In addition to their cholesterol-lowering action, statins have been suggested to exert anti-inflammatory activities. In this study we evaluate whether simvastatin could influence the production of pro-inflammatory cytokines (interleukin (IL)-6 and IL-8) and nitric oxide (NO) by activated human chondrocytes.METHODS:Human isolated chondrocytes and cartilage explants were pre-incubated with simvastatin (0.5, 5, 10 and 50 µmol/L) for 48 h. Then the cultures were stimulated with a mixture of IL-1Β and TNF-α (10 ng/mL) and co-incubated with simvastatin for an additional 48 h. A flow cytometric microsphere-based immunoassay was performed to detect cytokine secretion in the supernatants. NO production was quantified using the Griess assay.RESULTS:Simvastatin demonstrated significant dose-dependent inhibition of IL-6 and IL-8 production of isolated chondrocytes and cartilage explants up to 99% for IL-6 and up to 88% for IL-8 (p < 0.01). At the higher concentrations simvastatin decreased NO production by both isolated chondrocytes (up to 43%, p < 0.01) and cartilage explants (up to 30%, p < 0.01).CONCLUSIONS:This study demonstrates anti-inflammatory properties of simvastatin in chondrocytes in vitro, suggesting a potential cartilage-protective role for statins in arthritis.

【 授权许可】

Unknown