In vitro activation of human chondrocytes and synoviocytes by a human interleukin-1-like factor.
McGuire-Goldring MB., Meats JE., Wood DD., Ihrie EJ., Ebsworth NM., Russell RG.
Monocytes have been shown to secrete factors which stimulate the destruction of cartilage. Since one of the monocyte products, interleukin-1 (IL-1), has been shown to stimulate the release of collagenase and prostaglandin E from synoviocytes, we have investigated whether IL-1 is also responsible for chondrocyte activation. Purified preparations of IL-1 derived from human blood monocytes stimulated the production of prostaglandin E and plasminogen activator by human articular chondrocytes. After Sephadex G-75 chromatography, the lymphocyte-activating and the chondrocyte-activating activities of IL-1 eluted together in the regions corresponding to the void volume and to Kav = 0.2-0.3 (Mr 30,000-45,000) and Kav = 0.5-0.65 (Mr 12,000-17,000). The major peak of stimulating activity was the 12,000-17,000 dalton peak. Upon further analysis of the 12,000-17,000 dalton peak by isoelectric focusing, the major peak of lymphocyte-activating factor activity was recovered at a pI of 6.3 with a minor peak at 4.6-5.3. Similar patterns of activity were observed when the fractions were assayed for the stimulation of the production of prostaglandin E and plasminogen activator by human chondrocytes and of prostaglandin E by human synoviocytes. Treatment of the partially purified lymphocyte activating factor with phenylglyoxal reduced the thymocyte-stimulating activity 99% and the chondrocyte-stimulating activity 100%. These results suggest that IL-1 may stimulate the degradation of connective tissues during inflammation.