Modification of pro- and antiinflammatory cytokines and vascular-related molecules by tumor necrosis factor-a blockade in patients with rheumatoid arthritis.
OBJECTIVE
Analysis of serum concentrations and modifications of tumor necrosis factor-a (TNF-a), its soluble receptors (TNFR), interleukin 10 (IL-10), and vascular related molecules [soluble vascular cell adhesion molecule 1 (sVCAM-1), vascular endothelial growth factor (VEGF)] after therapy with methotrexate (MTX) and anti-TNF (infliximab) in patients with rheumatoid arthritis (RA).


METHODS
Thirty-six patients with RA and 20 healthy controls were included. Patients had been orally taking a stable dose of MTX of at least 12.5 mg/week for a minimum of 6 months before inclusion in the study. Twenty-five patients had shown a clinical response to MTX (MTX Group). The other 11 had shown an unsatisfactory response and presented with active RA; they were selected for additional treatment with infliximab (MTX + IFM Group). Disease activity score (DAS28), hemoglobin concentration, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and serum levels of TNF-a, soluble TNFR, IL-10, sVCAM-1 and VEGF were determined at baseline and prior to every infusion of infliximab (3 mg/kg) at 2, 6, 14, 22, and 30 weeks.


RESULTS
Although serum levels of TNF-a were similar in patients and controls, patients showed significantly higher concentrations of both soluble TNFR (sTNFR55 and sTNFR75), IL-10, sVCAM-1, and VEGF than healthy individuals. Significantly higher levels of sVCAM-1 and VEGF, but not of the other tested molecules, were detected in those with active disease. After infliximab treatment (MTX + IFM Group) there was a significant decrease in DAS28 and modified Health Assessment Questionnaire scores and ESR and CRP levels. Serum concentration of VEGF showed a significant decrease after infliximab, with levels comparable to those of patients with inactive RA, although VEGF continued to present higher values than in healthy controls.


CONCLUSIONS
Increased levels of vascular related molecules sVCAM-1 and VEGF are serum markers of active RA. The absence of normalization of levels of these molecules in patients with inactive RA could be one of the reasons response to therapy is only temporary.
Macías
Inmaculada
I
Rheumatology Service, Hospital Universitario Puerta del Mar, Cádiz, Spain.
García-Pérez
Sergio
S
Ruiz-Tudela
Mar
M
Medina
Fermín
F
Chozas
Nicolás
N
Girón-González
José A
JA
D000328:Adult; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D018501:Antirheumatic Agents / Q000008:administration & dosage*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology*; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D000069285:Infliximab; D016753:Interleukin-10 / Q000097:blood; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage*; D008875:Middle Aged; D018124:Receptors, Tumor Necrosis Factor / Q000097:blood; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000097:blood; D012074:Remission Induction; D016896:Treatment Outcome; D053319:Tumor Necrosis Factor Decoy Receptors; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D053319:Tumor Necrosis Factor Decoy Receptors; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D042461:Vascular Endothelial Growth Factor A; D016753:Interleukin-10; C069521:recombinant human tumor necrosis factor-binding protein-1; D000069285:Infliximab; D008727:Methotrexate