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英夫利昔单抗对类风湿关节炎患者趋化因子的影响。

The effect of infliximab on chemokines in patients with rheumatoid arthritis.

作者信息

Torikai Eiji, Kageyama Yasunori, Suzuki Motohiro, Ichikawa Tetsuya, Nagano Akira

机构信息

Department of Orthopaedic Surgery, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu, Japan.

出版信息

Clin Rheumatol. 2007 Jul;26(7):1088-93. doi: 10.1007/s10067-006-0453-5. Epub 2006 Nov 17.

Abstract

Rheumatoid arthritis (RA) is an autoimmune disease characterized by infiltration of lymphocytes, macrophages, and plasma cells into synovial membrane. The chemokines family promotes chemotactic activity in various leukocyte cell types. Chemokines thus play an essential role in the pathological formation of RA. The aim of the present study was to evaluate the influence of infliximab on serum levels of various chemokines. Twenty-four RA patients were involved in this study, which took place between March 2003 and February 2006. Infliximab was administered by intravenous infusion at a dosage of 3 mg/kg. All patients underwent general and physical examinations and routine blood and urinary analysis at the baseline, at 14 weeks, and at 30 weeks after the initial treatment. To determine whether serum and synovial fluid from RA also contained significant levels of chemokines compared with osteoarthritis patients (OA), GRO-alpha, MIP-1alpha, MIP-1beta and regulated on activation normal T cell expressed and secreted (RANTES) levels of serum and synovial fluid were measured by ELISA in 20 RA patients and 20 OA patients. GRO-alpha, MIP-1beta, and RANTES levels were significantly higher in RA compared with normal volunteers, while MIP-1alpha levels showed no significant differences. The mean GRO-alpha levels in serum from RA patients treated with infliximab decreased significantly after the initial treatment. The mean RANTES and MIP-1beta levels did not change significantly after the treatment. Infliximab treatment significantly lowered the serum GRO-alpha levels of RA patients. GRO-alpha is one of the crucial cytokines affected by infliximab treatment. The blocking therapy of RANTES and MIP-1beta combined with infliximab treatment may have an additional effect without competition in the TNFalpha cascade.

摘要

类风湿关节炎(RA)是一种自身免疫性疾病,其特征是淋巴细胞、巨噬细胞和浆细胞浸润滑膜。趋化因子家族促进各种白细胞类型的趋化活性。因此,趋化因子在RA的病理形成中起着至关重要的作用。本研究的目的是评估英夫利昔单抗对各种趋化因子血清水平的影响。本研究纳入了24例RA患者,研究时间为2003年3月至2006年2月。英夫利昔单抗通过静脉输注给药,剂量为3mg/kg。所有患者在初始治疗后的基线、14周和30周均接受了全身和体格检查以及血常规和尿常规分析。为了确定与骨关节炎患者(OA)相比,RA患者的血清和滑液中是否也含有显著水平的趋化因子,通过酶联免疫吸附测定法(ELISA)测量了20例RA患者和20例OA患者血清和滑液中的生长调节致癌基因-α(GRO-α)、巨噬细胞炎性蛋白-1α(MIP-1α)、巨噬细胞炎性蛋白-1β(MIP-1β)以及活化正常T细胞表达和分泌调节因子(RANTES)水平。与正常志愿者相比,RA患者的GRO-α、MIP-1β和RANTES水平显著更高,而MIP-1α水平无显著差异。接受英夫利昔单抗治疗的RA患者血清中的平均GRO-α水平在初始治疗后显著降低。治疗后RANTES和MIP-1β的平均水平没有显著变化。英夫利昔单抗治疗显著降低了RA患者的血清GRO-α水平。GRO-α是受英夫利昔单抗治疗影响的关键细胞因子之一。RANTES和MIP-1β的阻断疗法与英夫利昔单抗治疗联合使用可能在肿瘤坏死因子α(TNFα)级联反应中无竞争地产生额外效果。

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