ELEVATED SYNOVIAL-FLUID LEVELS OF INTERLEUKIN-6 AND TUMOR-NECROSIS-FACTOR ASSOCIATED WITH EARLY EXPERIMENTAL CANINE OSTEOARTHRITIS

Objective. To measure levels of cytokines, proteases, and glycosaminog lycans (GAG) in synovial fluid (SF) from the knees of animals with exp erimental osteoarthritis (OA) and from their contralateral (control) k nees, and to compare and correlate these values with each other as wel l as with measures of proteoglycan synthesis in the corresponding arti cular cartilage. This study will help to identify cytokines of potenti al importance in the early stages of the development of OA. Methods. O A was induced in 12 mature animals by sectioning the anterior cruciate ligament. After 3 months, SF from the operated and contralateral (con trol) knee joints was assayed for interleukin-6 (IL-6), tumor necrosis factor (TNF), IL-1, latent metalloproteinase, and sulfated GAG. Prote oglycan synthesis in the corresponding articular cartilage was also me asured. Results. IL-6 levels in SF from the operated joint compared wi th the control joint were significantly elevated in 11 of 12 animals. TNF levels were also elevated in 10 of 11 SF samples from operated joi nts, but to a lesser extent than those of IL-6. IL-1 and IL-1 inhibito rs were undetectable in either the operated or control joint SF. The G AG concentration was elevated in SF from experimental OA joints. This elevation correlated with that of TNF, but not IL-6. There was no sign ificant difference in the concentration of APMA-activatable metallopro teinase. The rate of proteoglycan synthesis was higher in the cartilag e from the operated joint in 8 of 12 animals, and the mean rate of syn thesis was significantly higher than in the control joint. There was a positive correlation between this increase in cartilage proteoglycan synthesis (operated versus control) and the increase in SF IL-6, but t here was no correlation with the levels of TNF or GAG. Conclusion. Thi s is the first study of SF levels of cytokines in early experimental O A. Our results show surprisingly high levels of IL-6 in operated joint s, where the cytokine could act directly on the chondrocytes, and thus play a role in mediating their responses to cartilage injury.