University of Utah Health Sciences Center, Salt Lake City, UT 84132-2409, USA.
Allergy. 2013 Jul;68(7):829-35. doi: 10.1111/all.12169. Epub 2013 Jun 6.
Several lines of evidence suggest that deficiency of eosinophils is not associated with any characteristic abnormality. Patients lacking eosinophils, in the setting of immunodeficiency or as a consequence of IgG-mediated eosinophil precursor destruction, do not display any distinguishing abnormalities related to eosinophil reduction. The observation that eosinophil-deficient mice do not display any distinctive syndrome or failure of their health is evidence that, under ordinary laboratory conditions, the eosinophil does not play a critical role in the well-being of mammals. Observations that monoclonal antibodies to interleukin-5 (IL-5) are well tolerated appear unsurprising in light of these findings. For example, patients with the hypereosinophilic syndrome have received mepolizumab, an anti-IL-5 monoclonal antibody, for as long as 6 years and have not developed any characteristic set of adverse events. Safety data for reslizumab, another anti-IL-5 monoclonal antibody, and benralizumab, a monoclonal antibody to the IL-5 receptor α-chain, are comparatively limited, especially for benralizumab, although reports of administration of these antibodies to humans suggest that they are well tolerated. Thus, data to the present suggest that reduction of eosinophils appears to have no characteristic ill effects on normal health, and monoclonal antibodies that deplete eosinophils have the potential to be widely employed in the treatment of eosinophil-associated diseases.
有几条证据表明,嗜酸性粒细胞缺乏与任何特征性异常无关。在免疫缺陷或由于 IgG 介导的嗜酸性粒细胞前体破坏的情况下缺乏嗜酸性粒细胞的患者,不会表现出与嗜酸性粒细胞减少相关的任何明显异常。观察到缺乏嗜酸性粒细胞的小鼠不会出现任何独特的综合征或健康问题,这表明在普通的实验室条件下,嗜酸性粒细胞在哺乳动物的健康中没有发挥关键作用。鉴于这些发现,观察到白细胞介素 5(IL-5)的单克隆抗体具有良好的耐受性似乎并不奇怪。例如,患有嗜酸性粒细胞增多综合征的患者已经接受了长达 6 年的抗 IL-5 单克隆抗体美泊利单抗治疗,并且没有出现任何特征性的不良事件。另一种抗 IL-5 单克隆抗体雷那利尤单抗和抗 IL-5 受体 α 链单克隆抗体贝那利珠单抗的安全性数据相对有限,特别是贝那利珠单抗,尽管这些抗体在人类中的应用报告表明它们具有良好的耐受性。因此,到目前为止的数据表明,嗜酸性粒细胞减少似乎对正常健康没有特征性的不良影响,并且消耗嗜酸性粒细胞的单克隆抗体有可能被广泛用于治疗嗜酸性粒细胞相关疾病。