Production of cytokines by chondrocytes and its role in proteoglycan degradation.

Increased populations of interleukin 1 (IL-1), tumor necrosis factor alpha (TNF-alpha), interleukin 6 (IL-6) and stromelysin (MMP-3) positive chondrocytes were found in osteoarthritic cartilage with immunoperoxidase microscopy using monospecific antibodies. Chondrocytic cytokine and MMP-3 productions were confirmed with tissue cultures of human osteoarthritic and healthy cartilage and monolayer cultures of rabbit articular chondrocytes. IL-6 production was induced by IL-1 alpha and TNF-alpha. The effects of these cytokines on proteoglycan degradation was also studied. While IL-1 alpha and TNF-alpha accelerated proteoglycan release and caseinase production by chondrocytes, IL-6 had no effect by itself and even depressed the effect of IL-1 alpha. Our results suggest that the cytokine network plays a crucial role in the chondrocyte mediated breakdown of cartilage.