Evidence that anti-tumor necrosis factor therapy with both etanercept and infliximab induces apoptosis in macrophages, but not lymphocytes, in rheumatoid arthritis joints: extended report.
Arthritis Rheum
; 52(1): 61-72, 2005 Jan.
Article
em En
| MEDLINE
| ID: mdl-15641091
ABSTRACT
OBJECTIVE:
Treatment of rheumatoid arthritis (RA) with tumor necrosis factor (TNF) antagonists is highly effective, but their mechanisms of action are not completely clear. Since anti-TNF therapy induces a decrease in synovial cellularity, this study focused on the modulation of RA synovial apoptosis following treatment with either soluble TNF receptor (etanercept) or TNF chimeric monoclonal antibody (infliximab).METHODS:
Apoptosis (TUNEL and active caspase 3 staining) and cell surface markers were evaluated by immunohistochemistry in synovial biopsy samples obtained before and after 8 weeks of treatment with etanercept (12 patients) or infliximab (9 patients). We also determined by flow cytometry the in vitro effect of etanercept and infliximab on apoptosis of RA mononuclear cells derived from the synovial fluid (SF) and peripheral blood (PB).RESULTS:
Eight weeks of treatment with etanercept and with infliximab significantly increased synovial apoptosis. This change was accompanied by a significant decrease in the synovial monocyte/macrophage population. The decrease in lymphocyte numbers did not reach statistical significance. In vitro, 24 hours of incubation with either etanercept or infliximab induced apoptosis of the SF monocyte/macrophage population. PB monocyte/macrophages were less susceptible to anti-TNF-mediated apoptosis. No changes in the rate of apoptosis were observed in the lymphocyte population derived from either SF or PB.CONCLUSION:
In RA patients, both etanercept and infliximab are able to induce cell type-specific apoptosis in the monocyte/macrophage population. This suggests a potential pathway that would account for the diminished synovial inflammation and the decreased numbers of synovial macrophages evident after TNF blockade.
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Base de dados:
MEDLINE
Assunto principal:
Artrite Reumatoide
/
Imunoglobulina G
/
Apoptose
/
Receptores do Fator de Necrose Tumoral
/
Antirreumáticos
/
Inibidores do Fator de Necrose Tumoral
/
Articulações
/
Macrófagos
/
Anticorpos Monoclonais
Tipo de estudo:
Clinical_trials
Limite:
Adult
/
Aged
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
Arthritis Rheum
Ano de publicação:
2005
Tipo de documento:
Article
País de afiliação:
Suécia