Endothelial progenitor cells in active rheumatoid arthritis:: effects of tumour necrosis factor and glucocorticoid therapy

Objectives: To study the effects of short-term intermediate dose glucocorticoid ( GC) therapy in patients with active rheumatoid arthritis ( RA) on circulating endothelial progenitor cells (EPC), which are known to influence cardiovascular risk, and to elucidate mechanisms potentially responsible for the reduction of EPCs in patients with active RA. Methods: EPCs were quantified in 29 patients with active RA by flow cytometry, colony forming unit (CFU) and circulating angiogenic cell (CAC) assays before and after 7 days of intermediate dose GC therapy. CFU from patients with RA and from healthy referents (HR) were cultured in vitro in the absence or presence of dexamethasone (Dex) and/or TNF. Results: After 1 week of GC therapy, EPC increased from 0.026 (SD 0.003)% to 0.053 ( SD 0.010)% ( p < 0.01), and from 12 ( SD 4) to 27 ( SD 7) CFU/well ( p, 0.02); CAC also increased from 7 ( SD 2) to 29 ( SD 8) cells/high power field ( p < 0.05). In parallel, disease activity decreased significantly after GC treatment. TNF serum levels also decreased from 36 ( SD 10) to 14 ( SD 6) pg/ml ( p < 0.0001). Addition of Dex to the RA CFU led to a significant increase of mean CFU counts, whereas addition of TNF induced a decrease of CFU. Conclusions: Our data indicate that TNF may be at least partly responsible for the reduction of EPC seen in patients with RA. Intermediate doses of GCs for a short period of time, apart from reducing disease activity, significantly increase circulating EPC.