Key Points IL-5 regulates development in BM and accumulation of eosinophils in the lung. IL-13 induces airway eosinophilia, AHR, and goblet cell metaplasia. Development and transmigration of eosinophils are synergistically affected by both cytokines. The type 2 cytokines IL-5, IL-13, and IL-4 play an important role in the induction and progression of asthma. According to the Global Initiative for Asthma guidelines, blood eosinophil numbers are one marker that helps to guide treatment decisions in patients suffering from severe forms of asthma. Effects of type 2 cytokines were analyzed, alone or in combination, on eosinophils in blood and other compartments and on the development of asthma symptoms. C57BL/6 mice received a single intranasal application of equimolar amounts of IL-5, IL-13, and IL-4, alone or in combination. Numbers, activation state, and migratory behavior of eosinophils in bone marrow (BM), blood, lung, and bronchoalveolar lavage as well as airway hyperresponsiveness and goblet cell metaplasia were evaluated. Only IL-13 was associated with airway eosinophilia, development of airway hyperresponsiveness, and goblet cell metaplasia, without any synergistic effects. IL-5 increased the number of eosinophils in BM and lung tissue but failed to affect structural changes. IL-4 had similar, but weaker, effects to IL-13. Cytokine combinations synergistically affected eosinophils but failed to enhance IL-13–driven effects on lung function or goblet cell metaplasia. IL-5 and IL-13 markedly increased eosinophil numbers locally in lung and airways and distally in blood and BM, whereas IL-5 and IL-4 only increased eosinophils in lung and BM. IL-13 together with IL-4 failed to demonstrate any synergistic effect. These insights into single and combined effects of type 2 cytokines on disease-driving mechanisms could improve understanding of the impact and effectiveness of new therapies in asthma.

中文翻译：

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2 型细胞因子对嗜酸性粒细胞和哮喘标志的单一和协同作用

关键点 IL-5 调节 BM 的发育和肺中嗜酸性粒细胞的积累。IL-13 诱导气道嗜酸性粒细胞增多、AHR 和杯状细胞化生。嗜酸性粒细胞的发育和迁移受两种细胞因子的协同影响。2 型细胞因子 IL-5、IL-13 和 IL-4 在哮喘的诱导和进展中起重要作用。根据全球哮喘倡议指南，血液嗜酸性粒细胞数量是一种有助于指导患有严重哮喘患者的治疗决策的标志物。单独或组合分析了 2 型细胞因子对血液和其他区室中的嗜酸性粒细胞以及哮喘症状发展的影响。C57BL/6 小鼠接受单次鼻内应用等摩尔量的 IL-5、IL-13 和 IL-4，单独或组合。数字，激活状态，评估了骨髓 (BM)、血液、肺和支气管肺泡灌洗液中嗜酸性粒细胞的迁移行为以及气道高反应性和杯状细胞化生。只有 IL-13 与气道嗜酸性粒细胞增多、气道高反应性的发展和杯状细胞化生有关，没有任何协同作用。IL-5 增加了 BM 和肺组织中嗜酸性粒细胞的数量，但未能影响结构变化。IL-4 与 IL-13 具有相似但较弱的作用。细胞因子组合协同影响嗜酸性粒细胞，但未能增强 IL-13 驱动对肺功能或杯状细胞化生的影响。IL-5 和 IL-13 显着增加局部肺和气道中的嗜酸性粒细胞数量，以及血液和骨髓中的远端嗜酸性粒细胞数量，而 IL-5 和 IL-4 仅增加肺和骨髓中的嗜酸性粒细胞数量。IL-13 和 IL-4 没有表现出任何协同作用。这些对 2 型细胞因子对疾病驱动机制的单一和联合影响的见解可以提高对新疗法对哮喘的影响和有效性的理解。