Effect of interleukin 17 on proteoglycan degradation in murine knee joints

Objective-To evaluate the effect of murine interleukin 17 (IL17) on cartila ge catabolism and joint inflammation by direct intra-articular injection of the cytokine into murine knee joints. Methods-Knees of normal C57 B1 mice were injected once or repeatedly with r ecombinant IL17 or IL1 beta. Inflammation was estimated by technetium-99m p ertechnetate (Tc-99) uptake and histological scoring of tissue sections. Pr oteoglycan depletion was evaluated by histological scoring of safranin O st ained sections. Effects on proteoglycan synthesis were studied by (SO4)-S-3 5 incorporation. Results-A single intra-articular injection of IL17 (10 ng/knee) produced ef fects very similar to those of IL1 beta (10 ng/knee). No inflammation was d etected at six or 24 hours by Tc-99 uptake. However, safranin O staining sh owed depletion of proteoglycan at 48 hours. Repeated injections of IL17 ind uced joint inflammation and cartilage proteoglycan depletion as shown by hi stological scoring. Unlike IL1 beta, proteoglycan depletion induced by IL17 seemed to be the result of increased degradation only, as no suppression o f (SO4)-S-35 incorporation was seen. Conclusion-These findings confirm, in vivo, the catabolic effects of IL17 o n cartilage. IL17 is thus the first T cell cytokine showing a direct catabo lic effect on cartilage in addition to stimulatory effects on macrophages a nd synoviocytes, making it a potentially important cytokine in the pathogen esis of arthritis.