Effect of anti-TNFalpha treatment on circulating endothelial progenitor cells (EPCs) in rheumatoid arthritis

Life Sci. 2006 Nov 17;79(25):2364-9. doi: 10.1016/j.lfs.2006.07.035. Epub 2006 Aug 5.

Abstract

Rheumatoid arthritis (RA) is associated with increased cardiovascular morbidity and mortality, which may be attenuated by anti-inflammatory treatment. Endothelial progenitor cells (EPCs) have the ability to differentiate into mature endothelium and have a potentially reparative role protecting against ischemia and atherosclerosis.

Objective: To investigate the effect of treatment with infliximab on the number and functional capacity of endothelial progenitor cells (EPCs) in patients with RA, as a possible mechanism for reducing cardiovascular morbidity in this disorder.

Patients: Active seropositive RA patients (N = 14) considered candidates for starting infliximab treatment, were recruited. Assessment, based on DAS-28, was performed before treatment and 14 days later. Peripheral blood mononuclear cells were isolated and EPC numbers evaluated by the colony-forming unit (CFU) method. Endothelial phenotyping of CFU was performed by immunofluorescence employing antibodies to Tie-2 VEGF-receptor 2, and CD31. EPC Functional properties were evaluated by fibronectin adherance.

Results: A significant 33.4% increase (p < 0.001) in EPC levels was observed after infliximab. A 60% increase was noted in the EPC differentiation scale, (p < 0.002) while a 37.6% increase was observed in mean EPC adhesion (p < 0.001). These changes were associated with a 17.5% decrease in the DAS-28 (p < 0.0001). A significant correlation was observed between the clinical response, reflected by changes in DAS-28 and the degree of increase in EPC CFUs.

Conclusion: A single dose of infliximab improved the number and functional properties of EPCs, in parallel with an early clinical effect, suggesting a possible mechanism by which anti-inflammatory treatment may reduce cardiovascular risk in RA patients.

MeSH terms

  • Antibodies, Monoclonal / therapeutic use*
  • Antigens, CD34 / metabolism
  • Antirheumatic Agents / therapeutic use*
  • Arthritis, Rheumatoid / blood*
  • Arthritis, Rheumatoid / drug therapy*
  • Blood Cell Count
  • Cell Adhesion / drug effects
  • Cell Differentiation / drug effects
  • Cells, Cultured
  • Colony-Forming Units Assay
  • Endothelium, Vascular / physiology*
  • Female
  • Fibronectins / metabolism
  • Humans
  • Infliximab
  • Male
  • Middle Aged
  • Platelet Endothelial Cell Adhesion Molecule-1 / metabolism
  • Receptor, TIE-2 / metabolism
  • Stem Cells / physiology*
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*
  • Tumor Necrosis Factor-alpha / metabolism
  • Vascular Endothelial Growth Factor Receptor-2 / metabolism

Substances

  • Antibodies, Monoclonal
  • Antigens, CD34
  • Antirheumatic Agents
  • Fibronectins
  • Platelet Endothelial Cell Adhesion Molecule-1
  • Tumor Necrosis Factor-alpha
  • Infliximab
  • Receptor, TIE-2
  • Vascular Endothelial Growth Factor Receptor-2