THERAPEUTIC EFFECT OF THE ANTI-FAS ANTIBODY ON ARTHRITIS IN HTLV-I FAX TRANSGENIC MICE

We have recently demonstrated Fas-mediated apoptosis in the synovium o f patients with rheumatoid arthritis (RA) and suggested that it may be one factor responsible for the regression of RA. To examine whether t he induction of apoptosis caused by anti-Fas mAb may play a potential role as a new therapeutic strategy for RA, we investigated the effect of anti-Fas mAb (RK-8) on synovitis in an animal model of RA, the huma n T cell leukemia virus type I(HTLV-I) tax transgenic mice. We report here that administration of anti-Fas mAb into mice intra-articularly i mproved the paw swelling and arthritis within 48 h. Immunohistochemica l study and in vitro culture studies showed that 35% of synovial fibro blasts, 75% of mononuclear cells, and some of polymorphonuclear leukoc ytes infiltrating in synovium underwent apoptosis by anti-Fas mAb. In situ nick end labeling analysis and electron microscope analysis clear ly showed that many cells in synovium were induced apoptosis by anti-F as mAb administration. However, local administration of anti-Fas mAb d id not produce systemic side effects. Results demonstrated that admini stration of anti-Fas mAb in arthritic joints of the HTLV-I tax transge nic mice produced improvement of arthritis. These findings suggest tha t local administration of anti-Fas mAb may represent a useful therapeu tic strategy for proliferative synovitis such as RA.