Therapeutic effect of the anti-Fas antibody on arthritis in HTLV-1 tax transgenic mice.
J Clin Invest
; 98(2): 271-8, 1996 Jul 15.
Article
em En
| MEDLINE
| ID: mdl-8755634
ABSTRACT
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Artrite Experimental
/
Membrana Sinovial
/
Vírus Linfotrópico T Tipo 1 Humano
/
Produtos do Gene tax
/
Receptor fas
/
Anticorpos Monoclonais
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
J Clin Invest
Ano de publicação:
1996
Tipo de documento:
Article
País de afiliação:
Japão