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.