The effect of tumor necrosis factor α and γ‐interferon on the resorption of human articular cartilage and on the production of prostaglandin e and of caseinase activity by human articular chondrocytes

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Abstract
In cultured human articular chondrocytes, addition of tumor necrosis factor α (TNFα1) stimulated caseinase activity over the range of 10−11M to 10−7M and stimulated prostaglandin E (PGE) production over the range of 10−10M to 10−7M. Maximal stimulation was observed at 10−8M TNFα for both activities. Gamma‐interferon (γ‐IFN) had a variable effect on PGE production and no significant effect on caseinase activity in articular chondrocyte cultures over a concentration range of 0.1–1,000 units/ml. Co‐incubation of TNFα with γ‐IFN enhanced PGE production and decreased caseinase activity. Concentrations as low as 1 unit/ml of γ‐IFN had significant effects on TNF‐stimulated production of PGE and on caseinase activity. Resorption of human articular cartilage was stimulated by TNFα (10−7M) and was inhibited by γ‐IFN (1,000 units/ml). It is possible that cartilage breakdown in vivo may be modulated by such interactions between cytokines.

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