title: Interleukin-6 is elevated in synovial fluid of patients with focal cartilage defects and stimulates cartilage matrix production in an in vitro regeneration model.
abstract: BACKGROUND
  This study aimed to determine whether, as in osteoarthritis, increased levels of interleukin-6 (IL-6) are present in the synovial fluid of patients with symptomatic cartilage defects and whether this IL-6 affects cartilage regeneration as well as the cartilage in the degenerated knee.
  
  
  METHODS
  IL-6 concentrations were determined by ELISA in synovial fluid and in conditioned media of chondrocytes regenerating cartilage. Chondrocytes were obtained from donors with symptomatic cartilage defects, healthy and osteoarthritic donors. The effect of IL-6 on cartilage regeneration and on metabolism of the resident cartilage in the knee was studied by both inhibition of endogenous IL-6 and addition of IL-6, in a regeneration model and in osteoarthritic explants in the presence of synovial fluid, respectively. Readout parameters were DNA and glycosaminoglycan (GAG) content and release. Differences between controls and IL-6 blocked or supplemented samples were determined by univariate analysis of variance using a randomized block design.
  
  
  RESULTS
  Synovial fluid of patients with symptomatic cartilage defects contained more IL-6 than synovial fluid of healthy donors (P = 0.001) and did not differ from osteoarthritic donors. IL-6 production of osteoarthritic chondrocytes during cartilage regeneration was higher than that of healthy and defect chondrocytes (P < 0.001). Adding IL-6 increased GAG production by healthy chondrocytes and decreased GAG release by osteoarthritic chondrocytes (P < 0.05). Inhibition of IL-6 present in osteoarthritic synovial fluid showed a trend towards decreased GAG content of the explants (P = 0.06).
  
  
  CONCLUSIONS
  Our results support a modest anabolic role for IL-6 in cartilage matrix production. Targeting multiple cytokines, including IL-6, may be effective in improving cartilage repair in symptomatic cartilage defects and osteoarthritis.
authors.forename: Anika I
authors.initials: AI
authors.lastname: Tsuchida
authors.forename: Michiel
authors.initials: M
authors.lastname: Beekhuizen
authors.forename: Marijn
authors.initials: M
authors.lastname: Rutgers
authors.forename: Gerjo J V M
authors.initials: GJ
authors.lastname: van Osch
authors.forename: Joris E J
authors.initials: JE
authors.lastname: Bekkers
authors.forename: Arjan G J
authors.initials: AG
authors.lastname: Bot
authors.forename: Bernd
authors.initials: B
authors.lastname: Geurts
authors.forename: Wouter J A
authors.initials: WJ
authors.lastname: Dhert
authors.forename: Daniel B F
authors.initials: DB
authors.lastname: Saris
authors.forename: Laura B
authors.initials: LB
authors.lastname: Creemers
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002358:Cartilage, Articular / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D002478:Cells, Cultured; D019902:Chondrocytes / Q000187:drug effects / Q000378:metabolism; D020219:Chondrogenesis / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism*; D006025:Glycosaminoglycans / Q000378:metabolism; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism* / Q000494:pharmacology; D008875:Middle Aged; D008954:Models, Biological; D010003:Osteoarthritis / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D012038:Regeneration / Q000187:drug effects; D013582:Synovial Fluid / Q000378:metabolism*; D046509:Tissue Culture Techniques; D055815:Young Adult; D000093242:Interleukin-6 Inhibitors
chemical_list: D006025:Glycosaminoglycans; D015850:Interleukin-6; D000093242:Interleukin-6 Inhibitors