Role of TNFα, in relation to IL-1 and IL-6 in the proteoglycan turnover of human articular cartilage

In both young and old human articular cartilage explants, TNFα induced a concentration-dependent, reversible suppression of the proteoglycan (PG) synthesis. Young cartilage was more sensitive to TNFα than old cartilage: 50% suppression of PG synthesis was reached at a TNFα concentration of 5 U/ml for young and 30 U/ml for old cartilage, whereas at 103 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 not enhanced. TNFα induced no detectable amounts of IL-1 (<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 TNFα-induced suppression of PG synthesis. The combination of TNFα and IL-1 led to an additive inhibition of PG synthesis which had no relationship to induced IL-6. TNFα was about 100-fold less active than IL-1. © 1991 Oxford University Press.