EFFECTS OF INTERLEUKIN-1-BETA ON INSULIN-LIKE GROWTH FACTOR-I AUTOCRINE PARACRINE AXIS IN CULTURED RAT ARTICULAR CHONDROCYTES/

Objective-To clarify the interaction of tissue destruction and repair of articular cartilage during inflammation, the effects of interleukin -1 beta (IL-1 beta) on the expression of insulin-like growth factor I (IGF-I), its receptor, and its binding proteins were examined. Methods -Articular chondrocytes from five week rats were cultured in serum fre e medium treated with IL-1 beta (1-100 U/ml) for 24 hours. The concent ration of IGF-1 in the conditioned medium was measured by RIA, and IGF BP were analysed by immunoligand blotting method. IGF-1 receptors were also examined by [I-125]IGF-I binding study. Results-IL-1 beta induce d the secretion of IGF-I and IGF-binding protein in chondrocytes; this was not inhibited by indomethacin (5 mu g/ml). IL-1 beta also increas ed the number ofIGF-I receptors but had no effect on receptor affinity . IL-1 beta inhibited chondrocyte proliferation, while exogenous IGF-I and growth hormone stimulated chondrocyte cell growth. IL-1 beta did not change IGF-I mRNA levels. Conclusion-IL-1 beta up-regulated the IG F-I autocrine/paracrine axis in cultured articular chondrocytes. These observations provide insight into the critical role played by IL-1 be ta in tissue destruction and repair, and into the direct interaction b etween cytokines and growth factors associated with inflammatory arthr opathy.