Effects of an interleukin-5 blocking monoclonal antibody on eosinophils, airway hyper-responsiveness, and the late asthmatic response

Effects of an interleukin-5 blocking monoclonal antibody on eosinophils, airway hyper-responsiveness, and the late asthmatic response
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DOI:
10.1016/s0140-6736(00)03496-6
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发表时间:
2000-12-23
期刊:
影响因子:
168.9
通讯作者:
Barnes, PJ
Barnes, PJ
中科院分区:
医学1区
文献类型:
--
作者:
Leckie, MJ;ten Brinke, A;Barnes, PJ

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背景白细胞介素-5(IL-5)是嗜酸性粒细胞形成所必需的,嗜酸性粒细胞被认为在哮喘和其他过敏性疾病的发病机制中起主要作用。我们的目的是评估IL-5单克隆抗体对轻度哮喘患者的血和痰嗜酸性粒细胞、气道高反应性和吸入性变应原的迟发哮喘反应的影响。其中单次静脉输注人源化的以2.5 mg/kg(n=8)或10.0 mg/kg(n =8)的剂量给予IL-5(IgG-κ)单克隆抗体(SB-240563)。治疗对吸入性过敏原的挑战,痰嗜酸性粒细胞,气道高反应性组胺的反应的影响进行了测量,在第1周和第4周与监测血液嗜酸性粒细胞计数长达16 weeks.Findings单克隆抗体对IL-5 towered平均血液嗜酸性粒细胞计数在第29天从0。25x10(9)/L(95%Cl 0 . 16-0 . 34)安慰剂组为0。04x10(9)/L(0 . 00-0 . 07)10 mg/kg组(p
Background Interleukin-5 (IL-5) is essential for the formation of eosinophils, which are thought to have a major role in the pathogenesis of asthma and other allergic diseases. We aimed to assess the effects of monoclonal antibody to IL-5 on blood and sputum eosinophils, airway hyperresponsiveness, and the late asthmatic reaction to inhaled allergen in patients with mild asthma.Methods We did a double-blind randomised placebo-controlled trial, in which a single intravenous infusion of humanised (IgG-kappa) monoclonal antibody to IL-5 (SB-240563) was given at doses of 2 .5 mg/kg (n=8) or 10 .0 mg/kg (n=8). The effects of treatment on responses to inhaled allergen challenge, sputum eosinophils, and airway hyper-responsiveness to histamine were measured at weeks 1 and 4 with monitoring of blood eosinophil counts for up to 16 weeks.Findings Monoclonal antibody against IL-5 towered the mean blood eosinophil count at day 29 from 0 . 25x10(9)/L (95% Cl 0 . 16-0 . 34) in the placebo group to 0 . 04x10(9)/L (0 . 00-0 . 07) in the 10 mg/kg group (p