Department of Pediatrics and Communicable Diseases, University of Michigan Medical School, Ann Arbor, MI, USA.
Clin Exp Allergy. 2012 Dec;42(12):1734-44. doi: 10.1111/cea.12005.
The mechanisms by which viruses induce asthma exacerbations are not well understood.
We characterized fluctuations in nasal aspirate cytokines during naturally occurring respiratory viral infections in children with asthma.
Sixteen children underwent home collections of nasal aspirates when they were without cold symptoms and again during self-reported respiratory illnesses. The presence of viral infection was ascertained by multiplex PCR. Cytokines were measured using multiplex immune assay. mRNA expression for selected markers of viral infection was measured using RT-PCR. A cumulative respiratory symptom score was calculated for each day of measurement. Generalized estimated equations were used to evaluate associations between viral infection and marker elevation, and between marker elevation and symptom score.
The 16 patients completed a total of 37 weeks of assessment (15 'well' weeks; 22 self-assessed 'sick' weeks). Viral infections were detected in 3 of the 'well' weeks and 17 of the 'sick' weeks (10 rhinovirus, three coronavirus, two influenza A, two influenza B, two respiratory syncytial virus, one parainfluenza). Compared to virus-negative well weeks, nasal aspirate IFN-γ, CXCL8/IL-8, CXCL10/IP-10, CCL5/RANTES, CCL11/eotaxin-1, CCL2/MCP-1, CCL4/MIP-1β, CCL7/MCP-3, and CCL20/MIP3α protein levels increased during virus-positive sick weeks. Only a subset of cytokines (IFN-γ, CXCL8, CCL2, CCL4, CCL5, and CCL20) correlated with self-reported respiratory tract symptoms. While many aspirates were dilute and showed no mRNA signal, viral infection significantly increased the number of samples that were positive for IFN-λ1, IFN-λ2/3, TLR3, RIG-I, and IRF7 mRNA.
We conclude that in children with asthma, naturally occurring viral infections apparently induce a robust innate immune response including expression of specific chemokines, IFNs, and IFN-responsive genes.
病毒引发哮喘加重的机制尚不清楚。
我们对哮喘患儿自然发生的呼吸道病毒感染期间鼻抽吸细胞因子的波动进行了特征描述。
16 名患儿在无感冒症状时和自述呼吸道疾病时进行家庭鼻抽吸采集。通过多重 PCR 确定病毒感染的存在。使用多重免疫测定法测量细胞因子。使用 RT-PCR 测量选定的病毒感染标志物的 mRNA 表达。为测量的每一天计算累积呼吸道症状评分。使用广义估计方程评估病毒感染与标志物升高之间以及标志物升高与症状评分之间的关联。
16 名患者共完成了 37 周的评估（15 周“健康”，22 周“生病”）。在 3 周的“健康”周和 17 周的“生病”周中检测到病毒感染（10 例鼻病毒、3 例冠状病毒、2 例流感 A、2 例流感 B、2 例呼吸道合胞病毒、1 例副流感）。与病毒阴性的健康周相比，鼻抽吸 IFN-γ、CXCL8/IL-8、CXCL10/IP-10、CCL5/RANTES、CCL11/eotaxin-1、CCL2/MCP-1、CCL4/MIP-1β、CCL7/MCP-3 和 CCL20/MIP3α 蛋白水平在病毒阳性的生病周内升高。只有一部分细胞因子（IFN-γ、CXCL8、CCL2、CCL4、CCL5 和 CCL20）与自述呼吸道症状相关。虽然许多抽吸物很稀释，没有 mRNA 信号，但病毒感染显著增加了 IFN-λ1、IFN-λ2/3、TLR3、RIG-I 和 IRF7 mRNA 呈阳性的样本数量。
我们得出结论，在哮喘患儿中，自然发生的病毒感染显然会引起强烈的先天免疫反应，包括特定趋化因子、IFN 和 IFN 反应基因的表达。
