Klimiuk P A, Sierakowski S, Domyslawska I, Chwiecko J
Department of Rheumatology and Internal Diseases, Medical University of Bialystok, Bialystok, Poland.
Clin Exp Rheumatol. 2006 Sep-Oct;24(5):529-33.
We studied the effects of the multiple infusions of infliximab, a chimeric anti-tumor necrosis factor alpha (anti-TNF-alpha) antibody, on the serum chemokines levels in patients with active rheumatoid arthritis (RA).
RA patients were supposed to receive 9 infusions of infliximab (3mg/kg) at weeks 0, 2, 6, and every 8 weeks thereafter with the same dose. All patients continued treatment with methotrexate (MTX) (7.5-20mg/week). Serum concentrations of interleukin-8 (IL-8), RANTES (regulated upon activation, normal T cell expressed and secreted) and monocyte chemoattractant protein-1 (MCP-1) were assessed by ELISA at weeks 0, 2, 6, 14, 38, prior to infusion, and additionally at week 62.
Initial infusion of infliximab caused reduction in serum IL-8, RANTES and MCP-1 (in all cases p < 0.001) levels. Subsequent infliximab administrations also significantly decreased serum chemokines levels, but was less effective. Prior to the first infliximab infusion serum concentrations of studied chemokines correlated with markers of RA activity such as the erythrocyte sedimentation rate (ESR) or CRP levels, number of swollen joints and disease activity score (DAS). Following next drug infusions such associations were far less significant. Infliximab treatment induced a significant reduction in the number of monocytes observed through the whole study (in all cases p < 0.05).
Anti-TNF-alpha antibody therapy accompanied by MTX, beside a rapid clinical improvement, reduced serum chemokines concentrations in RA patients. Subsequent administrations of infliximab sustained chemokines decrease, although to a lesser extent than the first two dose of infliximab.
我们研究了多次输注英夫利昔单抗(一种嵌合型抗肿瘤坏死因子α(抗TNF-α)抗体)对活动性类风湿关节炎(RA)患者血清趋化因子水平的影响。
RA患者应在第0、2、6周接受9次英夫利昔单抗(3mg/kg)输注,此后每8周输注相同剂量。所有患者继续接受甲氨蝶呤(MTX)(7.5 - 20mg/周)治疗。在第0、2、6、14、38周输注前以及第62周通过酶联免疫吸附测定法(ELISA)评估白细胞介素-8(IL-8)、调节激活正常T细胞表达和分泌因子(RANTES)以及单核细胞趋化蛋白-1(MCP-1)的血清浓度。
首次输注英夫利昔单抗导致血清IL-8、RANTES和MCP-1水平降低(所有病例p < 0.001)。随后的英夫利昔单抗给药也显著降低了血清趋化因子水平,但效果较差。在首次输注英夫利昔单抗之前,所研究趋化因子的血清浓度与RA活动指标相关,如红细胞沉降率(ESR)或CRP水平、肿胀关节数量和疾病活动评分(DAS)。在接下来的药物输注后,这种关联远不那么显著。在整个研究过程中,英夫利昔单抗治疗导致观察到的单核细胞数量显著减少(所有病例p < 0.05)。
抗TNF-α抗体疗法联合MTX,除了能快速改善临床症状外,还降低了RA患者的血清趋化因子浓度。随后的英夫利昔单抗给药维持了趋化因子的降低,尽管程度低于前两剂英夫利昔单抗。