Interleukin-10/Interleukin-5 Responses at Birth Predict Risk for Respiratory Infections in Children with Atopic Family History
Interleukin-10/Interleukin-5 Responses at Birth Predict Risk for Respiratory Infections in Children with Atopic Family History
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DOI：
10.1164/rccm.200803-438oc
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发表时间：
2009-02-01
影响因子：
24.7
通讯作者：
Holt, Patrick G.
中科院分区：
文献类型：
--
作者：
Zhang, Guicheng;Rowe, Julie;Holt, Patrick G.
理由：生命早期的呼吸道感染与喘息性细支气管炎的风险相关，特别是对于特应性高风险的儿童。潜在机制尚不清楚，但怀疑与该年龄段免疫系统功能不成熟导致的宿主防御反应失衡有关。 目的：评估嗜酸性粒细胞营养性 IL-5 和强效抗炎细胞因子 IL-10 对生命早期感染风险的贡献。 测量和主要结果：我们前瞻性监测了 198 名 5 岁以下高危儿童的队列，记录每次急性呼吸道感染发作并对它们进行分类按严重程度。我们测量了脐带血 T 细胞产生 IL-10 和 IL-5 的能力，并将这些功能与随后的感染史联系起来。 IL-10 和 IL-5 分别与感染的抵抗力和易感性相关。当通过为每个受试者生成 IL-10/IL-5 反应比来考虑组合时，可以看到这两种细胞因子的最大对比效果。相对于更具抵抗力的高 IL-10/低 IL-5 表型，低 IL-10/高 IL-5 T 细胞反应表型与对所有级别的急性呼吸道感染的易感性密切相关。结论：出生时 T 细胞过量产生 IL-5 与随后发生严重呼吸道感染的风险增加有关，并且伴随 IL-10 的产生可以减弱这种风险。潜在机制可能涉及 IL-10 介导的 IL-5 依赖性嗜酸性粒细胞诱导炎症的反馈抑制，这是生命早期宿主抗病毒反应的常见特征。
Rationale: Respiratory infections in early life are associated with risk for wheezing bronchiolitis, especially in children at high risk of atopy. The underlying mechanisms are unknown, but are suspected to involve imbalance(s) in host defense responses against pathogens stemming from functional immaturity of the immune system in this age group.Objectives: To assess the contribution of eosinophil-trophic IL-5, and the potent antiinflammatory cytokine IL-10, to risk for infection in early life.Measurements and Main Results: We prospectively monitored a cohort of 198 high-risk children to age 5 years, recording every acute respiratory infection episode and classifying them by severity. We measured cord blood T-cell capacity to produce IL-10 and IL-5, and related these functions to subsequent infection history. IL-10 and IL-5 were associated, respectively, with resistance versus susceptibility to infections. The greatest contrasting effects of these two cytokines were seen when they were considered in combination by generating IL-10/IL-5 response ratios for each subject. The low IL-10/high IL-5T-cell response phenotype was strongly associated with susceptibility to all grades of acute respiratory infection, relative to the more resistant high IL-10/low IL-5 phenotype.Conclusions: Excessive production of IL-5 by T cells at birth is associated with heightened risk for subsequent severe respiratory infections, and this risk is attenuated by concomitant IL-10 production. The underlying mechanisms may involve IL-10-mediated feedback inhibition of IL-5-dependent eosinophil-induced inflammation, which is a common feature of host antiviral responses in early life.