title: Role of TNF alpha, in relation to IL-1 and IL-6 in the proteoglycan turnover of human articular cartilage.
abstract: In both young and old human articular cartilage explants, TNF alpha induced a concentration-dependent, reversible suppression of the proteoglycan (PG) synthesis. Young cartilage was more sensitive to TNF alpha than old cartilage: 50% suppression of PG synthesis was reached at a TNF alpha concentration of 5 U/ml for young and 30 U/ml for old cartilage, whereas at 10(3) U/ml the PG synthesis of young cartilage was blocked and that of old cartilage suppressed by 80%. These inhibition levels of PG synthesis resulted in 25% PG depletion of the explants after 8 days of culture. The release of cartilage PG was not enhanced. TNF alpha induced no detectable amounts of IL-1 (less than 0.01 U) in young or old cartilage but did induce IL-6 production. The induced amounts of IL-6 were higher in young than in old cartilage but no dose-dependency was evident. Antibodies to neither IL-1 nor IL-6 had any influence on the TNF alpha-induced suppression of PG synthesis. The combination of TNF alpha and IL-1 led to an additive inhibition of PG synthesis which had no relationship to induced IL-6. TNF alpha was about 100-fold less active than IL-1.
authors.affiliation: Department of Rheumatology, University Hospital Utrecht, The Netherlands.
authors.forename: B
authors.initials: B
authors.lastname: Wilbrink
authors.forename: J J
authors.initials: JJ
authors.lastname: Nietfeld
authors.forename: W
authors.initials: W
authors.lastname: den Otter
authors.forename: J L
authors.initials: JL
authors.lastname: van Roy
authors.forename: J W
authors.initials: JW
authors.lastname: Bijlsma
authors.forename: O
authors.initials: O
authors.lastname: Huber-Bruning
mesh_terms: D000375:Aging / Q000378:metabolism; D002358:Cartilage, Articular / Q000378:metabolism*; D003470:Culture Media; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism*; D011509:Proteoglycans / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology / Q000502:physiology*
chemical_list: D003470:Culture Media; D007375:Interleukin-1; D015850:Interleukin-6; D011509:Proteoglycans; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha