Klimiuk P A, Sierakowski S, Domyslawska I, Chwiecko J
Department of Rheumatology and Internal Diseases, Medical University of Bialystok, Bialystok, Poland.
Scand J Rheumatol. 2009 Nov-Dec;38(6):439-44. doi: 10.3109/03009740903079321.
Endothelium and adhesion molecules are engaged in the pathogenesis of rheumatoid arthritis (RA). This study was undertaken to analyse the effect of etanercept on the levels of soluble cell adhesion molecules (sCAMs) and vascular endothelial growth factor (VEGF) in patients with active RA.
Patients were receiving 50 mg/week of subcutaneous etanercept and 10-25 mg/week of methotrexate (MTX). Serum levels of soluble intercellular adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule-1 (sVCAM-1), E-selectin (sE-selectin), and VEGF were measured by enzyme-linked immunosorbent assay (ELISA) in 18 RA patients (prior to injection) at 0, 3, 6, 9, and 12 months.
A decrease in serum levels of sICAM-1 (p<0.001), sVCAM-1 (p<0.01), sE-selectin (p<0.01), and VEGF (p<0.001) was observed in RA patients after 3 months of treatment with etanercept. Six months of therapy with etanercept prolonged the suppression of serum sICAM-1 (p<0.01) and even more remarkably diminished sVCAM-1, sE-selectin, and VEGF (in all cases p<0.001) concentrations as compared to baseline (month 0). Treatment also effectively diminished sICAM-1, sVCAM-1, and VEGF levels at months 9 and 12 (in all cases p<0.001), and less significantly sE-selectin (p<0.05 at month 9 and p<0.01 at month 12). The Disease Activity Score including a 28-joint count (DAS28) measured at 3, 6, 9, and 12 months decreased significantly compared to baseline (in all cases p<0.001).
Our study shows that, besides a rapid suppression of disease activity, serum sCAM and VEGF concentrations are downregulated following anti-tumour necrosis factor alpha (TNFalpha) therapy combined with MTX. Prolonged treatment with etanercept sustained or even more remarkably diminished the sCAM and VEGF serum concentrations.
内皮细胞和黏附分子参与类风湿关节炎（RA）的发病机制。本研究旨在分析依那西普对活动期RA患者可溶性细胞黏附分子（sCAMs）和血管内皮生长因子（VEGF）水平的影响。
患者接受每周50mg皮下注射依那西普和每周10 - 25mg甲氨蝶呤（MTX）治疗。通过酶联免疫吸附测定（ELISA）法，在18例RA患者（注射前）的第0、3、6、9和12个月测量血清可溶性细胞间黏附分子-1（sICAM-1）、血管细胞黏附分子-1（sVCAM-1）、E-选择素（sE-选择素）和VEGF的水平。
依那西普治疗3个月后，RA患者血清sICAM-1（p<0.001）、sVCAM-1（p<0.01）、sE-选择素（p<0.01）和VEGF（p<0.001）水平下降。与基线（第0个月）相比，依那西普治疗6个月可延长血清sICAM-1的抑制时间（p<0.01），并更显著降低sVCAM-1、sE-选择素和VEGF的浓度（所有情况p<0.001）。在第9和12个月，治疗也有效降低了sICAM-1、sVCAM-1和VEGF水平（所有情况p<0.001），而sE-选择素降低程度较小（第9个月p<0.05，第12个月p<0.01）。与基线相比，在第3、6、9和12个月测量的包括28个关节计数的疾病活动评分（DAS28）显著降低（所有情况p<0.001）。
我们的研究表明，除了快速抑制疾病活动外，抗肿瘤坏死因子α（TNFα）联合MTX治疗后血清sCAM和VEGF浓度下调。依那西普的长期治疗维持或更显著降低了sCAM和VEGF的血清浓度。
