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.