title: Endothelial progenitor cells in active rheumatoid arthritis: effects of tumour necrosis factor and glucocorticoid therapy.
abstract: OBJECTIVE
  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.
authors.affiliation: Division of Rheumatology, Department of Internal Medicine III, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria. johannes.grisar@meduniwien.ac.at
authors.forename: Johannes
authors.initials: J
authors.lastname: Grisar
authors.forename: Daniel
authors.initials: D
authors.lastname: Aletaha
authors.forename: Carl W
authors.initials: CW
authors.lastname: Steiner
authors.forename: Theresa
authors.initials: T
authors.lastname: Kapral
authors.forename: Sabine
authors.initials: S
authors.lastname: Steiner
authors.forename: Marcus
authors.initials: M
authors.lastname: Säemann
authors.forename: Ilse
authors.initials: I
authors.lastname: Schwarzinger
authors.forename: Barbara
authors.initials: B
authors.lastname: Buranyi
authors.forename: Günter
authors.initials: G
authors.lastname: Steiner
authors.forename: Josef S
authors.initials: JS
authors.lastname: Smolen
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology; D018501:Antirheumatic Agents / Q000494:pharmacology; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay / Q000379:methods; D003907:Dexamethasone / Q000494:pharmacology; D042783:Endothelial Cells / Q000187:drug effects*; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D000069285:Infliximab; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D011239:Prednisolone / Q000627:therapeutic use*; D013234:Stem Cells / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood* / Q000494:pharmacology
chemical_list: D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; D005938:Glucocorticoids; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D003907:Dexamethasone; D011239:Prednisolone; D000069285:Infliximab