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


E.J. Dombrecht, J.F. Van Offel, C.H. Bridts, D.G. Ebo, V. Seynhaeve, A.J. Schuerwegh, W.J. Stevens, L.S. De Clerck

 

CER3049
2007 Vol.25, N°4
PI 0534, PF 0539
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PMID: 17888208 [PubMed]

Abstract

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.

Rheumatology Article