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.