The late, but not early, asthmatic response is dependent on IL-5 and correlates with eosinophil infiltration
The late, but not early, asthmatic response is dependent on IL-5 and correlates with eosinophil infiltration
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DOI：
10.1172/jci7010
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发表时间：
1999-08-01
影响因子：
15.9
通讯作者：
Gelfand, EW
中科院分区：
文献类型：
--
作者：
Cieslewicz, G;Tomkinson, A;Gelfand, EW
早期反应（EPR）和晚期反应（LPR）是支气管哮喘的特征性特征，尽管每种反应的发病机制尚未完全确定。开发了EPR和LPR的鼠模型以研究IL-5和嗜酸性粒细胞在两种应答的发展中的作用。在初始腹腔致敏和对卵清蛋白（OVA）的气道激发后，通过额外暴露于OVA激发小鼠。抗原激发后5-30分钟观察到以气道反应性一过性增加为特征的EPR。该反应之后是LPR，在激发后6小时达到最大值，其特征为气道反应性增加和显著的肺嗜酸性粒细胞增多。色甘酸盐和沙丁胺醇可阻断EPR，而色甘酸盐和氢化可的松可阻断LPR。在用变应原激发前，给予抗IL-5抗体可阻止嗜酸性粒细胞流入肺组织，并消除LPR，但不消除EPR。这些结果表明，IL-5和嗜酸性粒细胞是必不可少的LPR的发展，但不是EPR，在这个模型中。
Early-phase reactions (EPRs) and late-phase reactions (LPRs) are characteristic features of bronchial asthma, although the pathogenetic mechanisms responsible for each of the responses are not fully defined. A murine model of EPRs and LPRs was developed to investigate the role of IL-5 and eosinophils in development of both responses. After initial intraperitoneal sensitization and airway challenge to ovalbumin (OVA), mice were provoked by additional exposure to OVA. An EPR, characterized by a transient increase in airway responsiveness, was observed 5-30 minutes after antigen provocation. This response was followed by an LPR that reached its maximum at 6 hours after challenge and was characterized by increased airway responsiveness and significant lung eosinophilia. The EPR was blocked by cromoglycate and albuterol, whereas the LPR was abolished by cromoglycate and hydrocortisone. Before provocation with allergen, administration of anti-IL-5 antibody prevented the influx of eosinophils into the lung tissue and abolished the LPR but not EPR. These results suggest that IL-5 and eosinophils are essential for development of the LPR, but not EPR, in this model.