Reduction of soluble adhesion molecules (sICAM-1, sVCAM-1, and sE-selectin) and vascular endothelial growth factor levels in serum of rheumatoid arthritis patients following multiple intravenous infusions of infliximab.
BACKGROUND
The purpose of this study was to determine the effect of repeated infusions of infliximab, a chimeric anti-tumor necrosis factor (anti-TNF)-alpha antibody, on the levels of soluble adhesion molecules and vascular endothelial growth factor (VEGF) in patients with active rheumatoid arthritis (RA).


METHODS
The treatment design consisted of 9 infusions of infliximab (3 mg/kg) at weeks 0, 2, 6, and every 8 weeks thereafter. All patients had been receiving methotrexate (MTX; 7.5-20 mg/week). Serum levels of soluble intercellular adhesion molecule (sICAM)-1, vascular cell adhesion molecule (sVCAM)-1, E-selectin (sE-selectin), and VEGF were measured by ELISA at weeks 0, 2, 6, 14, and 38 prior to infusion, and at week 62.


RESULTS
A remarkable decrease in serum sICAM-1 (p<0.001), sVCAM-1 (p<0.01), sE-selectin (p<0.01) and VEGF (p<0.001) levels was observed in RA patients after the initial dose of infliximab. The second administration of the drug was followed by an even more significant suppression of serum sICAM-1, sVCAM-1, sE-selectin, and VEGF (p<0.001 in all cases). Further infliximab infusions also significantly reduced serum soluble adhesion molecules and VEGF concentrations, although these were less effective. Infliximab treatment induced a significant decrease in the number of monocytes observed until the end of the study.


CONCLUSIONS
Our study, besides a rapid suppression of disease activity, showed that serum soluble adhesion molecules and VEGF concentrations are down-regulated following anti-TNF-alpha antibody therapy combined with MTX. Repeated doses of infliximab sustained the reductions in the soluble adhesion molecules and VEGF concentrations, although they were less effective than the first and second infusions of infliximab.
Klimiuk
Piotr A
PA
Department of Rheumatology and Internal Diseases, Medical University of Białystok, Białystok, Poland. klimp@amb.edu.pl
Sierakowski
Stanisław
S
Domysławska
Izabela
I
Fiedorczyk
Małgorzata
M
Chwiećko
Justyna
J
D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000378:metabolism; D019040:E-Selectin / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D000069285:Infliximab; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood*; D008727:Methotrexate / Q000008:administration & dosage; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood*; D042461:Vascular Endothelial Growth Factor A / Q000097:blood*
D000911:Antibodies, Monoclonal; D019040:E-Selectin; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D042461:Vascular Endothelial Growth Factor A; D018799:Intercellular Adhesion Molecule-1; D000069285:Infliximab; D008727:Methotrexate