title: Influence of simvastatin on the production of pro-inflammatory cytokines and nitric oxide by activated human chondrocytes.
abstract: 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.
authors: Faculty of Medicine, Department of Immunology, Allergology and Rheumatology, University of Antwerp, Antwerp, Belgium.
authors: E J
authors: EJ
authors: Dombrecht
authors: J F
authors: JF
authors: Van Offel
authors: C H
authors: CH
authors: Bridts
authors: D G
authors: DG
authors: Ebo
authors: V
authors: V
authors: Seynhaeve
authors: A J
authors: AJ
authors: Schuerwegh
authors: W J
authors: WJ
authors: Stevens
authors: L S
authors: LS
authors: De Clerck
mesh_terms: 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
chemical_list: 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