Anti-interieukin-5 (mepolizumab) therapy for hypereosinophilic syndromes
Anti-interieukin-5 (mepolizumab) therapy for hypereosinophilic syndromes
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DOI：
10.1016/j.jaci.2003.10.049
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发表时间：
2004-01-01
影响因子：
14.2
通讯作者：
Rothenberg, ME
中科院分区：
文献类型：
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作者：
Garrett, JK;Jameson, SC;Rothenberg, ME
背景：IL-5 是一种细胞因子，关键参与调节嗜酸性粒细胞的多个方面，包括嗜酸性粒细胞的产生、激活和组织募集。因此，IL-5 可能参与嗜酸性粒细胞增多综合征的发病机制，这是一组治疗不良的多种疾病，其特征是持续的外周血和/或组织嗜酸性粒细胞增多。 目的：我们旨在评估针对 IL-5 的人源化阻断单克隆抗体（美泊利单抗）在多种形式的嗜酸性粒细胞增多症患者中的安全性和有效性。 方法：我们进行了一项抗 IL-5 开放标签试验，其中 4 名患有嗜酸性粒细胞增多综合征（定义为外周血和/或组织嗜酸性粒细胞增多）的患者每隔 4 周注射 3 次静脉注射剂量（10 mg/kg，最大 750 mg）。在 28 周内测量治疗对安全性、嗜酸性粒细胞水平（外周血和/或患病组织中）、肺功能和生活质量的影响。结果：所有患者对抗 IL-5 的耐受性良好，尽管持续进行全身糖皮质激素治疗，但外周血嗜酸性粒细胞计数仍降低。最后一剂抗 IL-5 后，循环嗜酸性粒细胞计数的下降持续至少 12 周。此外，抗 IL-5 改善了临床和生活质量测量。在一名患有显着组织嗜酸性粒细胞增多（嗜酸性粒细胞性食管炎）的患者中，抗 IL-5 导致组织嗜酸性粒细胞水平降低 10 倍。结论：这些结果表明，抗 IL-5 是安全的，可有效降低嗜酸性粒细胞水平，并且对患有各种嗜酸性粒细胞增多综合征的患者具有潜在的糖皮质激素节约作用。因此，抗 IL-5 可能对嗜酸性粒细胞增多综合征具有显着的治疗潜力。
Background: IL-5 is a cytokine critically involved in regulating several aspects of eosinophils including their production, activation, and tissue recruitment. As such, IL-5 may be involved in the pathogenesis of hypereosinophilic syndromes, a group of poorly treated diverse disorders characterized by sustained peripheral blood and/or tissue eosinophilia.Objective: We aimed to assess the safety and efficacy of a humanized blocking monoclonal antibody against IL-5 (mepolizumab) in patients with several forms of hypereosinophilic syndromes.Methods: We performed an open-label trial of anti-IL-5 in which 3 intravenous doses (10 mg/kg, maximum 750 mg) were administered at 4-week intervals to 4 patients with hypereosinophilic syndromes (defined by peripheral blood and/or tissue eosinophilia). The effects of treatment on safety, eosinophil levels (in peripheral blood and/or diseased tissue), pulmonary function, and quality of life were measured over a 28-week period.Results: Anti-IL-5 was well tolerated in all patients and lowered peripheral blood eosinophil counts despite ongoing systemic glucocorticoid therapy. The decline in circulating eosinophil counts was sustained for at least 12 weeks after the last dose of anti-IL-5. In addition, anti-IL-5 improved clinical and quality of life measurements. In one patient with striking tissue eosinophilia (eosinophilic esophagitis), anti-IL-5 resulted in a 10-fold reduction in tissue eosinophil levels.Conclusions: These results suggest that anti-IL-5 is safe, effective in lowering eosinophil levels, and has potential glucocorticoid-sparing effects in patients with a variety of hypereosinophilic syndromes. As such, anti-IL-5 may have significant therapeutic potential for hypereosinophilic syndromes.