Klimiuk Piotr A, Sierakowski Stanisław, Domysławska Izabela, Fiedorczyk Małgorzata, Chwiećko Justyna
Department of Rheumatology and Internal Diseases, Medical University of Białystok, Białystok, Poland.
Arch Immunol Ther Exp (Warsz). 2004 Jan-Feb;52(1):36-42.
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).
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.
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.
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.
本研究的目的是确定重复输注英夫利昔单抗（一种嵌合抗肿瘤坏死因子（抗TNF）-α抗体）对活动性类风湿关节炎（RA）患者可溶性黏附分子和血管内皮生长因子（VEGF）水平的影响。
治疗方案包括在第0、2、6周输注9次英夫利昔单抗（3mg/kg），此后每8周输注一次。所有患者均一直在接受甲氨蝶呤（MTX；7.5 - 20mg/周）治疗。在输注前的第0、2、6、14和38周以及第62周，通过酶联免疫吸附测定法（ELISA）测量血清可溶性细胞间黏附分子（sICAM）-1、血管细胞黏附分子（sVCAM）-1、E-选择素（sE-选择素）和VEGF的水平。
在RA患者中，首次输注英夫利昔单抗后，血清sICAM-1（p<0.001）、sVCAM-1（p<0.01）、sE-选择素（p<0.01）和VEGF（p<0.001）水平显著降低。第二次给药后，血清sICAM-1、sVCAM-1、sE-选择素和VEGF受到更显著的抑制（所有病例p<0.001）。进一步输注英夫利昔单抗也显著降低了血清可溶性黏附分子和VEGF浓度，尽管效果较差。英夫利昔单抗治疗导致直至研究结束时观察到的单核细胞数量显著减少。
我们的研究除了迅速抑制疾病活动外，还表明抗TNF-α抗体联合MTX治疗后血清可溶性黏附分子和VEGF浓度下调。重复剂量的英夫利昔单抗维持了可溶性黏附分子和VEGF浓度的降低，尽管其效果不如首次和第二次输注英夫利昔单抗。
