Lacy P, Weller P F, Moqbel R
Pulmonary Research Group, University of Alberta, Edmonton, Canada.
J Allergy Clin Immunol. 2001 Dec;108(6):895-900. doi: 10.1067/mai.2001.120194.
The International Eosinophil Symposium in Banff was a timely gathering of leading experts to discuss the precise role of eosinophils in allergic asthma. The meeting followed hard on the heels of a report suggesting that eosinophils might be redundant in late-phase responses in asthma, inasmuch as treatment of asthmatic patients with humanized anti-IL-5 in clinical trials failed to modify bronchial hyperresponsiveness. Mouse models of allergic asthma were also cited for failing to show a consistent proinflammatory role for the eosinophil in asthma. Presentations at this meeting included a reevaluation of murine models of asthma, which exhibit substantial differences from human disease. The inability of murine eosinophils to degranulate either in vivo or in vitro was shown to present a major obstacle in asthma research; this is in sharp contrast to human eosinophils, which readily degranulate in response to stimuli. Degranulation from eosinophils was proposed to be a crucial event in human airway hyperresponsiveness. Major advances were presented in the understanding of molecular and intracellular pathways regulating eosinophil priming, activation, and mediator secretion. Recruitment and activation of eosinophils might be regulated by other immunoregulatory agents as well as IL-5, including eotaxin. Future clinical trials might benefit from focusing on dual inhibition of IL-5 and eotaxin to ensure the removal of the effects of activated eosinophils from the body.
在班夫举行的国际嗜酸性粒细胞研讨会及时汇聚了顶尖专家，以探讨嗜酸性粒细胞在过敏性哮喘中的确切作用。此次会议紧随着一份报告召开，该报告表明嗜酸性粒细胞在哮喘的晚期反应中可能是多余的，因为在临床试验中用人源化抗IL-5治疗哮喘患者未能改变支气管高反应性。过敏性哮喘的小鼠模型也因未能显示嗜酸性粒细胞在哮喘中具有一致的促炎作用而被提及。本次会议的报告包括对哮喘小鼠模型的重新评估，这些模型与人类疾病存在显著差异。结果表明，小鼠嗜酸性粒细胞在体内或体外均无法脱颗粒，这在哮喘研究中是一个主要障碍；这与人类嗜酸性粒细胞形成鲜明对比，人类嗜酸性粒细胞在受到刺激时很容易脱颗粒。嗜酸性粒细胞脱颗粒被认为是人类气道高反应性中的一个关键事件。在理解调节嗜酸性粒细胞启动、激活和介质分泌的分子和细胞内途径方面取得了重大进展。嗜酸性粒细胞的募集和激活可能受其他免疫调节因子以及IL-5（包括嗜酸性粒细胞趋化因子）的调控。未来的临床试验可能会受益于聚焦对IL-5和嗜酸性粒细胞趋化因子的双重抑制，以确保从体内消除活化嗜酸性粒细胞的影响。
