title: Comparative and combined effects of interleukin 6, interleukin 1 beta, and tumor necrosis factor alpha on proteoglycan metabolism of human articular chondrocytes cultured in agarose.
abstract: OBJECTIVE
  To study the effects of recombinant tumor necrosis factor alpha (TNF-alpha), interleukin 1 beta (IL-1 beta) and interleukin 6 (IL-6) on proteoglycan metabolism of isolated chondrocytes.
  
  
  METHODS
  Human articular cartilage cells were cultured in agarose gel. In these culture conditions, chondrocytes keep their phenotypic stability. They release cartilage specific proteoglycans into the surrounding artificial matrix. Proteoglycan synthesis was measured by the incorporation of 35sulfate (35S).
  
  
  RESULTS
  TNF-alpha and IL-1 beta depressed proteoglycan synthesis and induced proteoglycan degradation. The effects of both cytokines were additive, when used in submaximal doses. No mutual induction of TNF-alpha and IL-1 beta was shown, but both cytokines stimulated the chondrocytes to release IL-6, up to 100,000 pg/ml. Equal amounts of human recombinant IL-6 did not affect proteoglycan synthesis. IL-6 did not alter proteoglycan quality, nor did it modulate the IL-1 beta activities on proteoglycan metabolism.
  
  
  CONCLUSIONS
  These findings illustrate the role of IL-1 beta and TNF-alpha in cartilage degradation and suggest that the role of the large amounts of IL-6 released in response to IL-1 in chronic arthritis is not directly protective with regard to proteoglycan metabolism.
authors.affiliation: Department of Rheumatology, University Hospital, Ghent, Belgium.
authors.forename: A M
authors.initials: AM
authors.lastname: Malfait
authors.forename: G
authors.initials: G
authors.lastname: Verbruggen
authors.forename: E M
authors.initials: EM
authors.lastname: Veys
authors.forename: J
authors.initials: J
authors.lastname: Lambert
authors.forename: L
authors.initials: L
authors.lastname: De Ridder
authors.forename: M
authors.initials: M
authors.lastname: Cornelissen
mesh_terms: D001168:Arthritis / Q000209:etiology; D002358:Cartilage, Articular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D002478:Cells, Cultured; D016207:Cytokines / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D007375:Interleukin-1 / Q000008:administration & dosage / Q000494:pharmacology; D015850:Interleukin-6 / Q000008:administration & dosage / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008854:Microscopy, Electron; D011509:Proteoglycans / Q000378:metabolism*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D012685:Sepharose; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000494:pharmacology
chemical_list: D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D008070:Lipopolysaccharides; D011509:Proteoglycans; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D012685:Sepharose