title: Monosodium urate crystal induced macrophage inflammation is attenuated by chondroitin sulphate: pre-clinical model for gout prophylaxis?
abstract: BACKGROUND
  Chondroitin Sulphate (CS), a natural glycosaminoglycan of the extracellular matrix, has clinical benefit in symptomatic osteoarthritis but has never been tested in gout. In vitro, CS has anti-inflammatory and positive effects on osteoarthritic chondrocytes, synoviocytes and subchondral bone osteoblasts, but its effect on macrophages is unknown. The purpose of our study was to evaluate the in vitro effects of CS on monosodium urate (MSU)-stimulated cytokine production by macrophages.
  
  
  METHODS
  THP-1 monocytes were differentiated into mature macrophages using a phorbol ester, pretreated for 4 hours with CS in a physiologically achievable range of concentrations (10-200 μg/ml) followed by MSU crystal stimulation for 24 hours. Cell culture media were analyzed by immunoassay for factors known to be upregulated during gouty inflammation including IL-1β, IL-8 and TNFα. The specificity of inflammasome activation by MSU crystals was tested with a caspase-1 inhibitor (0.01 μM-10 μM).
  
  
  RESULTS
  MSU crystals ≥10 mg/dl increased macrophage production of IL-1β, IL-8 and TNFα a mean 7-, 3- and 4-fold respectively. Induction of IL-1β by MSU was fully inhibited by a caspase-1 inhibitor confirming inflammasome activation as the mechanism for generating this cytokine. In a dose-dependent manner, CS significantly inhibited IL-1β (p = 0.003), and TNFα (p = 0.02) production from macrophages in response to MSU. A similar trend was observed for IL-8 but was not statistically significant (p = 0.41).
  
  
  CONCLUSIONS
  CS attenuated MSU crystal induced macrophage inflammation, suggesting a possible role for CS in gout prophylaxis.
authors.forename: Eric W
authors.initials: EW
authors.lastname: Orlowsky
authors.forename: Thomas V
authors.initials: TV
authors.lastname: Stabler
authors.forename: Eulàlia
authors.initials: E
authors.lastname: Montell
authors.forename: Josep
authors.initials: J
authors.lastname: Vergés
authors.affiliation: Department of Medicine, Division of Rheumatology, Duke University School of Medicine, Durham, NC, USA. vbk@duke.edu.
authors.forename: Virginia Byers
authors.initials: VB
authors.lastname: Kraus
mesh_terms: D002460:Cell Line; D002809:Chondroitin Sulfates / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical / Q000379:methods; D006073:Gout / Q000473:pathology / Q000517:prevention & control; D006801:Humans; D007249:Inflammation / Q000473:pathology / Q000517:prevention & control; D008264:Macrophages / Q000187:drug effects* / Q000473:pathology; D009000:Monocytes / Q000187:drug effects / Q000473:pathology; D014527:Uric Acid / Q000633:toxicity*
chemical_list: D014527:Uric Acid; D002809:Chondroitin Sulfates