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Effect of interleukin 17 on proteoglycan degradation in murine knee joints
J Dudler1, N Renggli-Zulliger, N Busso
1Service de Rhumatologie, Médecine Physique et Rééducation, Centre Hospitalier Universitaire Vaudois, CHUV - 1011 Lausanne, Switzerland. jdudler@chuv.hospvd.ch
Objective:
To evaluate the effect of murine interleukin 17 (IL17) on cartilage catabolism and joint inflammation by direct intra-articular injection of the cytokine into murine knee joints.
Methods:
Knees of normal C57 Bl mice were injected once or repeatedly with recombinant IL17 or IL1beta. Inflammation was estimated by technetium-99m pertechnetate ((99)Tc) uptake and histological scoring of tissue sections. Proteoglycan depletion was evaluated by histological scoring of safranin O stained sections. Effects on proteoglycan synthesis were studied by (35)SO(4) incorporation.
Results:
A single intra-articular injection of IL17 (10 ng/knee) produced effects very similar to those of IL1beta (10 ng/knee). No inflammation was detected at six or 24 hours by (99)Tc uptake. However, safranin O staining showed depletion of proteoglycan at 48 hours. Repeated injections of IL17 induced joint inflammation and cartilage proteoglycan depletion as shown by histological scoring. Unlike IL1beta, proteoglycan depletion induced by IL17 seemed to be the result of increased degradation only, as no suppression of (35)SO(4) incorporation was seen.
Conclusion:
These findings confirm, in vivo, the catabolic effects of IL17 on cartilage. IL17 is thus the first T cell cytokine showing a direct catabolic effect on cartilage in addition to stimulatory effects on macrophages and synoviocytes, making it a potentially important cytokine in the pathogenesis of arthritis.