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Therapy with soluble TNF receptor (etanercept) induces apoptosis in rheumatoid arthritis (RA) synovium
Arthritis Res Ther volume 5, Article number: 34 (2003)
This study evaluates modulation of rheumatoid arthritis (RA) synovial apoptosis by therapy with the soluble tumor necrosis factor (TNF) alpha receptor (etanercept).
Apoptosis (TUNEL [transferase-mediated UTP end labeling] combined with morphology), cell-surface markers (CD3, CD68, CD163, Fas), FLIP and granzyme B were evaluated by immunohistochemistry in synovial biopsies from 12 RA patients before and after 8 weeks of treatment with etanercept. Moreover, the in vitro effect of etanercept on FLIP expression and on the death of mononuclear cells (MNCs) derived from synovial fluid (SF) was determined in five RA patients by flow cytometry.
Etanercept treatment increased synovial apoptosis and decreased the number of CD68-positive and CD163-positive monocyte/macrophages and FLIP expression (P < 0.05). No significant changes were observed for the expression of CD3, Fas and granzyme B. In vitro, low concentrations of etanercept (1 and 10 μg/ml) increased cell death (P < 0.05) in the SF CD14-positive monocyte/macrophage population after 24 hours' incubation, while higher concentrations (100 μg/ml) had no effect. FLIP expression in this population did not change after in vitro culture with either low or high doses. The in vitro culture with etanercept did not induce any changes in FLIP expression or apoptosis level in SF CD3-positive cells.
Therapy with etanercept at clinically relevant concentrations increased RA synovial monocyte/macrophage apoptosis, suggesting an alternate pathway to explain the decrease in synovial cellularity observed after anti-TNF therapy.
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Catrina, A., Trollmo, C., Lampa, J. et al. Therapy with soluble TNF receptor (etanercept) induces apoptosis in rheumatoid arthritis (RA) synovium. Arthritis Res Ther 5, 34 (2003) doi:10.1186/ar664
- Rheumatoid Arthritis
- Tumor Necrosis Factor
- Rheumatoid Arthritis Patient
- Synovial Fluid