Effect of thrombin inhibition on synovial inflammation in antigen induced arthritis

doi:10.1136/ard.59.10.781

Annals of the Rheumatic Diseases 2000;59:781-787; doi:10.1136/ard.59.10.781

Ann Rheum Dis 2000;59:781-787 ( October )

Extended report

Effect of thrombin inhibition on synovial inflammation in antigen induced arthritis Pierre Alain Varisco^a, Veronique Péclat^a, Karen van Ness^a, Angelika Bischof-Delaloye^b, Alexander So^a, Nathalie Busso^a

^a Laboratoire de Rhumatologie, Centre Hospitalier Universitaire Vaudois, 1011 Lausanne, Switzerland, ^b Département de Médecine Nucléaire, Centre Hospitalier Universitaire Vaudois

Correspondence to: Dr Nathalie Busso, CHUV, Laboratoire de Rhumatologie, Nestlé 05-5029, 1011 Lausanne, Switzerland Email: Nathalie.Busso{at}chuv.hospvd.ch

Accepted for publication 7 April 2000

OBJECTIVE $---$ To determine the effect of the thrombin inhibitor, hirudin, on the pathogenesis of murine antigen induced arthritis(AIA).
METHODS $---$ AIA was induced by intra-articular injection of methylated bovine serum albumin in the knee joints of previously immunisedmice. Hirudin (injected subcutaneously 3 × 200 µg/mouse/day) wasgiven over 13 days, starting three days before arthritis onset,and its anticoagulant effect monitored by clotting times. Arthritisseverity was evaluated by technetium-99m (^99mTc) uptake in the knee joints and by histological scoring. Inaddition, intra-articular fibrin deposition was examined by immunohistochemistry,and synovial cytokine mRNA expression measured by RNaseprotection.
RESULTS $---$ Joint inflammation, measured by ^99mTc uptake, was significantly reduced in hirudin treated mice at days 7 and 10 after arthritisonset. Histologically, synovial thickness was markedly decreasedin hirudin treated mice compared with untreated ones. By contrast,no difference in articular cartilage proteoglycan content wasfound between both groups. Intra-articular fibrin deposition andsynovial interleukin 1 $beta$ mRNA levels, were slightly reduced (~20%)in arthritic joints from hirudin treated mice compared with untreatedones at day 10 ofAIA.
CONCLUSION $---$ Hirudin reduces joint inflammation associated with AIA by fibrin-dependent and independentmechanisms.

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