220 BRADYKININ, THROUGH B 2 RECEPTORS, ACTIVATES THE RELEASE OF THE CYTOKINE INTERLEUKIN 6, THE CHEMOKINE INTERLEUKIN 8, AND THE METALLOPROTEINASE 3 IN HUMAN KNEE CHONDROCYTES

Abstract

Results: Cartilage cultured in the presence of blood showed a decrease of proteoglycan synthesis rate of 70%, an increase of proteoglycan release of 100%, and a decrease of proteoglycan content of 15% after 16 days of culture (all p<0.05). This blood-induced damage of the cartilage matrix was limited by IL-4 in a clear dose-dependent way. Addition of 100 ng/ml IL-4 during blood-exposure reduced the proteoglycan synthesis rate with only 45%, and decreased the proteoglycan release with 30% compared to control (all p<0.05). Moreover, proteoglycan content was normalized. The combination of IL-4 and IL-10 was clearly more protective against damage caused by blood. This was especially evident for the proteoglycan synthesis which was completely normalized. Furthermore, treatment with a combination of the two cytokines was significantly better than the effect of IL-4 and IL-10 alone (p<0.05). Conclusions: Besides IL-10, as shown previously, also IL-4 protects against blood-induced cartilage damage. The combination of these two cytokines is clearly the most protective. In addition to the direct effects on cartilage, both cytokines are synergistic in inhibition of inflammation. As such, this justifies further evaluation of the combination of IL-4 and IL-10 in prevention and treatment of blood-induced joint damage.