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a Service de
Rhumatologie, Médecine Physique et Rééducation, Centre
Hospitalier Universitaire Vaudois, CHUV - 1011 Lausanne, Switzerland, b Division of Arthritis Research, The Scripps
Research Institute, La Jolla, CA 92037, USA
Correspondence to: Dr Dudler Email: jdudler{at}chuv.hospvd.ch
Accepted for publication 15 February 2000
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.
METHODSKnees of
normal C57 Bl mice were injected once or repeatedly with recombinant
IL17 or IL1
. Inflammation was estimated by technetium-99m
pertechnetate (99Tc) 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 35SO4 incorporation.
RESULTSA single
intra-articular injection of IL17 (10 ng/knee) produced effects very
similar to those of IL1 (10 ng/knee). No inflammation was detected
at six or 24 hours by 99Tc 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 IL1,
proteoglycan depletion induced by IL17 seemed to be the result of
increased degradation only, as no suppression of
35SO4 incorporation was seen.
CONCLUSIONThese
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.
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