Influence of simvastatin on the production of pro-inflammatory cytokines and nitric oxide by activated human chondrocytes.
OBJECTIVE
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 micromol/L) for 48 h. Then the cultures were stimulated with a mixture of IL-1Beta and TNF-alpha (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.
Dombrecht
E J
EJ
Faculty of Medicine, Department of Immunology, Allergology and Rheumatology, University of Antwerp, Antwerp, Belgium.
Van Offel
J F
JF
Bridts
C H
CH
Ebo
D G
DG
Seynhaeve
V
V
Schuerwegh
A J
AJ
Stevens
W J
WJ
De Clerck
L S
LS
D000328:Adult; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001168:Arthritis / Q000378:metabolism; D002356:Cartilage / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D019902:Chondrocytes / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D053583:Interleukin-1beta / Q000494:pharmacology; D015850:Interleukin-6 / Q000096:biosynthesis*; D016209:Interleukin-8 / Q000096:biosynthesis*; D008875:Middle Aged; D009569:Nitric Oxide / Q000096:biosynthesis*; D010446:Peptide Fragments / Q000494:pharmacology; D019821:Simvastatin / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D000893:Anti-Inflammatory Agents; D053583:Interleukin-1beta; D015850:Interleukin-6; D016209:Interleukin-8; D010446:Peptide Fragments; D014409:Tumor Necrosis Factor-alpha; C052994:interleukin-1beta (163-171); D009569:Nitric Oxide; D019821:Simvastatin