SCH527123, a novel CXCR2 antagonist, inhibits ozone-induced neutrophilia in healthy subjects
SCH527123, a novel CXCR2 antagonist, inhibits ozone-induced neutrophilia in healthy subjects
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DOI：
10.1183/09031936.00048509
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发表时间：
2010-03-01
影响因子：
24.3
通讯作者：
Magnussen, H.
中科院分区：
文献类型：
--
作者：
Holz, O.;Khalilieh, S.;Magnussen, H.
SCH 527123是一种新型的选择性CXC趋化因子受体2拮抗剂，在动物模型中抑制中性粒细胞活化并调节中性粒细胞运输，其特征可能有益于治疗不平衡的肺嗜中性粒细胞增多症，如慢性阻塞性肺病。这项原理验证研究的目的是确定SCH 527123是否抑制臭氧诱导的中性粒细胞在健康人体中的募集。在一项随机、双盲、安慰剂对照、三向交叉研究中，口服SCH 527123（50 mg，每日一次，4天）、泼尼松龙（50 mg，一次）或安慰剂交替使用2周洗脱。18名健康的臭氧应答者（痰中性粒细胞增加>20%）在最后一次治疗剂量后1小时接受臭氧激发试验（250 ppb，3小时间歇运动）。在激发后3 h诱导痰。SCH 527123治疗后，臭氧激发导致痰中性粒细胞计数（0.13 x 10（6）.mL（-1））显著低于泼尼松龙（0.84 x 10（6）.mL（-1; p
SCH527123 is a novel, selective CXC chemokine receptor 2 antagonist that inhibits neutrophil activation and modulates neutrophil trafficking in animal models, characteristics that may be beneficial in the treatment of conditions with unbalanced pulmonary neutrophilia, such as chronic obstructive pulmonary disease. The purpose of this proof-of-principle study was to determine whether SCH527123 inhibits ozone-induced neutrophil recruitment in healthy humans.In a randomised, double-blind, placebo-controlled, three-way crossover study, oral SCH527123 (50 mg once daily, 4 days), prednisolone (50 mg once), or placebo was alternated with 2-week washouts. 18 healthy ozone responders (>20% increase in sputum neutrophils) underwent ozone challenge tests (250 ppb, 3 h intermittent exercise) 1 h after the last treatment dose. Sputum was induced at 3 h post-challenge.After SCH527123 treatment, the ozone challenge resulted in significantly lower sputum neutrophil counts (0.13 x 10(6).mL(-1)) compared with prednisolone (0.84 x 10(6).mL(-1); p