Therapeutic effect of the anti-Fas antibody on arthritis in HTLV-1 tax transgenic mice.
We have recently demonstrated Fas-mediated apoptosis in the synovium, of patients with rheumatoid arthritis (RA) and suggested that it may be one factor responsible for the regression of RA. To examine whether the 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 human T cell leukemia virus type I (HTLV-1) tax transgenic mice. We report here that administration of anti-Fas mAb into mice intra-articularly improved the paw swelling and arthritis within 48 h. Immunohistochemical study and in vitro culture studies showed that 35% of synovial fibroblasts, 75% of mononuclear cells, and some of polymorphonuclear leukocytes infiltrating in synovium underwent apoptosis by anti-Fas mAb. In situ nick end labeling analysis and electron microscope analysis clearly showed that many cells in synovium were induced apoptosis by anti-Fas mAb administration. However, local administration of anti-Fas mAb did not produce systemic side effects. Results demonstrated that administration of anti-Fas mAb in arthritic joints of the HTLV-1 tax transgenic mice produced improvement of arthritis. These findings suggest that local administration of anti-Fas mAb may represent a useful therapeutic strategy for proliferative synovitis such as RA.
Fujisawa
K
K
Division of Rheumatology and Immunology, Institute of Medical Science, St. Marianna University School of Medicine, Japan.
Asahara
H
H
Okamoto
K
K
Aono
H
H
Hasunuma
T
T
Kobata
T
T
Iwakura
Y
Y
Yonehara
S
S
Sumida
T
T
Nishioka
K
K
D000410:Alanine Transaminase / Q000097:blood; D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D017209:Apoptosis; D001169:Arthritis, Experimental / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D001219:Aspartate Aminotransferases / Q000097:blood; D006224:Cricetinae; D003433:Crosses, Genetic; D004487:Edema; D016356:Gene Products, tax / Q000096:biosynthesis* / Q000235:genetics; D015368:Human T-lymphotropic virus 1 / Q000235:genetics*; D006801:Humans; D007074:Immunoglobulin G / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D013583:Synovial Membrane / Q000276:immunology / Q000473:pathology* / Q000503:physiopathology; D019014:fas Receptor / Q000276:immunology*
D000911:Antibodies, Monoclonal; D016356:Gene Products, tax; D007074:Immunoglobulin G; D019014:fas Receptor; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase