The effect of tumor necrosis factor alpha and gamma-interferon on the resorption of human articular cartilage and on the production of prostaglandin E and of caseinase activity by human articular chondrocytes.

In cultured human articular chondrocytes, addition of tumor necrosis factor alpha (TNF alpha) stimulated caseinase activity over the range of 10(-11) M to 10(-7) M and stimulated prostaglandin E (PGE) production over the range of 10(-10) M to 10(-7) M. Maximal stimulation was observed at 10(-8)M TNF alpha for both activities. Gamma-interferon (gamma-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 TNF alpha with gamma-IFN enhanced PGE production and decreased caseinase activity. Concentrations as low as 1 unit/ml of gamma-IFN had significant effects on TNF-stimulated production of PGE and on caseinase activity. Resorption of human articular cartilage was stimulated by TNF alpha (10(-7) M) and was inhibited by gamma-IFN (1,000 units/ml). It is possible that cartilage breakdown in vivo may be modulated by such interactions between cytokines.