THE ROLE OF IL-4 AND IL-6 IN IL-1-DEPENDENT CARTILAGE MATRIX DEGRADATION

The objective of this paper was to study the effects of interleukin 4 (IL-4) and interleukin 6 (IL-6) on cartilage matrix degradation, the p roduction of chondroitin-4-sulphate (C4S) and chondroitin-6-sulphate ( C6S), metalloproteinase (stromelysin 1 = MMP-3) and metalloproteinase inhibitor (TIMP-1) production. Cartilage matrix degradation was assaye d the release of (SO4)-S-35 from chondrocyte cultures. TIMP-1 and MMP- 3 were measured by ELISA. C6S and C4S were measured by HPLC analysis. IL-1 beta significantly enhanced C4S production and significantly supp ressed C6S production. Thus, the C4S/C6S ratio was significantly enhan ced by IL-1 beta, and significantly suppressed by IL-4. IL-4 removed t he suppressing effects of IL-1 beta for C6S and the enhancing effects of IL-1 beta for the C4S/C6S ratio. Whereas IL-I beta stimulated the p roduction of MMP-3, IL-4 and IL-6 had no effect on enzyme activity. IL -4, but not IL-6, removed the enhancing effects of IL-1 beta for MMP-3 . In contrast, IL-4 and IL-6 significantly enhanced TIMP-1 production in chondrocytes. IL-4, but not IL-6, also significantly suppressed IL- 1 beta-mediated cartilage matrix degradation. On the other hand, IL-6 significantly suppressed spontaneous cartilage matrix degradation whic h is supposed to be mediated by the autocrine IL-1 mechanisms. In conc lusion our results suggest that IL-4 and IL-6 both protect the cartila ge matrix degradation induced by IL-1.