title: Growth factor activity of IL-6 in the synovial fluid of patients with rheumatoid arthritis.
abstract: OBJECTIVE
  We set out to determine whether the ability of synovial fluids (SF) in patients with rheumatoid arthritis (RA) to facilitate the proliferation of synovial tissue-derived fibroblastic cell lines was related to the presence of growth factors and/or cytokines.
  
  
  METHODS
  The growth factor activity of 20 RA SF was measured by their ability to induce anchorage-independent growth of the rat NRK-49F (49F) fibroblastic strain. The presence of transforming growth factor-beta (TGF-beta) and platelet-derived growth factor (PDGF) was also assessed using neutralising anti-TGF-beta or anti-PDGF-AB mAbs. Cytokines were measured by functional assays or ELISA:
  
  
  RESULTS
  We observed a correlation between growth factor activity and the IL-6 levels in SF. Both were correlated to the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels in SF and serum. IL-6 (at concentrations above 10(4) U/ml), synergized with growth factors in the induction of the anchorage independent (AI) growth of 49F cells. Pretreatment of SF with a neutralising anti-IL-6 mAb substantially reduced the capacity of these SF to induce AI growth of 49F cells, confirming the growth factor activity of IL-6 in this test. In contrast, IL-6 alone or in association with PDGF, epidermal growth factor (EGF) or TGF-beta had no effect on the anchored growth of synovial tissue-derived fibroblasts, and treatment of SF with a neutralising anti-IL-6 mAb did not affect their ability to increase the growth rate of synovial tissue-derived fibroblasts.
  
  
  CONCLUSIONS
  These results strongly suggest that IL-6 is responsible for the observed correlation between the growth factor activity of SF and inflammatory indexes such as ESR and CRP. However, neither IL-6 nor PDGF were responsible for the observed positive effect of SF on synovial fibroblastic cell lines.
authors.affiliation: INSERM U291, Montpellier, France.
authors.forename: S
authors.initials: S
authors.lastname: Monier
authors.forename: T
authors.initials: T
authors.lastname: Rème
authors.forename: C
authors.initials: C
authors.lastname: Cognot
authors.forename: Q L
authors.initials: QL
authors.lastname: Gao
authors.forename: A
authors.initials: A
authors.lastname: Travaglio-Encinoza
authors.forename: M
authors.initials: M
authors.lastname: Cuchacovich
authors.forename: J P
authors.initials: JP
authors.lastname: Gaillard
authors.forename: C
authors.initials: C
authors.lastname: Jorgensen
authors.forename: J
authors.initials: J
authors.lastname: Sany
authors.forename: A
authors.initials: A
authors.lastname: Dupuy d'Angeac
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000503:physiopathology*; D001799:Blood Sedimentation; D002097:C-Reactive Protein / Q000378:metabolism; D002455:Cell Division / Q000502:physiology; D002460:Cell Line; D004815:Epidermal Growth Factor / Q000502:physiology*; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D051379:Mice; D008875:Middle Aged; D010982:Platelet-Derived Growth Factor / Q000502:physiology*; D051381:Rats; D013582:Synovial Fluid / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000502:physiology*
chemical_list: D015850:Interleukin-6; D010982:Platelet-Derived Growth Factor; D016212:Transforming Growth Factor beta; D004815:Epidermal Growth Factor; D002097:C-Reactive Protein