ROLE OF OXYGEN RADICALS AND IL-6 IN IL-1-DEPENDENT CARTILAGE MATRIX DEGRADATION

It has been suggested that IL-1 produces cartilage matrix degradation by metalloproteinases such as collagenase and that such degradation is regulated by metalloproteinase inhibitors. In the present study, the effects of IL-6 and oxygen radical scavengers on cartilage matrix degr adation were studied. Superoxide dismutase, catalase, or methionine al l significantly inhibited cartilage matrix degradation both in IL-1 be ta-stimulated and unstimulated experimental conditions. Both 10 mM EDT A and 100 nM tissue inhibitor of metalloproteinase (TIMP) significantl y inhibited cartilage matrix degradation. The addition of methionine s ignificantly inhibited collagenase activity produced in the culture su pernatants of chondrocytes stimulated with IL-1 beta. IL-6 significant ly suppressed cartilage matrix degradation produced spontaneously or b y IL-1 beta stimulation in chondrocytes. IL-6 inhibited superoxide pro duction by chondrocytes both in IL-1 beta-stimulated or unstimulated c onditions. These results suggest that oxygen radicals are involved in cartilage matrix degradation mediated by both paracrine and autocrine IL-1 mechanisms and that oxygen radical-mediated activation of collage nase in chondrocytes may explain the mechanisms of how oxygen radicals are involved in cartilage matrix degradation. IL-6 inhibited superoxi de production in chondrocytes and thus inhibited cartilage matrix degr adation.