Type 1 and type 2 cytokine imbalance in acute respiratory syncytial virus bronchiolitis
Type 1 and type 2 cytokine imbalance in acute respiratory syncytial virus bronchiolitis
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DOI：
10.1164/rccm.200210-1148oc
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发表时间：
2003-09-15
影响因子：
24.7
通讯作者：
Warner, JO
中科院分区：
文献类型：
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作者：
Legg, JP;Hussain, IR;Warner, JO
我们通过分析婴儿鼻灌洗液和刺激的外周血单个核细胞的细胞因子水平，研究了婴儿对自然呼吸道合胞病毒（RSV）感染的体内免疫反应。88名父母中至少有一方患有过敏性哮喘的婴儿在出生后的第一个冬天进行了前瞻性研究。28名婴儿有上呼吸道感染，其中检测到RSV，其中9人出现急性细支气管炎的症状。采用定量聚合酶链反应检测鼻灌洗液标本的干扰素γ、白细胞介素(IL)-4、IL-10和IL-12水平，并检测RSV载量。从受刺激的外周血单个核细胞中提取信使RNA (mRNA)，并通过聚合酶链反应测定干扰素- γ、IL-4、IL-12和IL-18 mRNA的水平。分析细胞因子谱与临床结果的关系。与单纯上呼吸道感染的婴儿相比，急性毛细支气管炎患儿鼻灌洗液中IL-4/干扰素比值在发病1-2天（p = 0.014）和5-7天（p = 0.001）均升高。急性细支气管炎患者在第1-2天IL-10/IL-12比值升高（p = 0.0015）。急性毛细支气管炎患儿外周血单核细胞IL-18 mRNA水平降低（p = 0.019）， IL-4/干扰素比值升高（p = 0.01）。初始RSV载量无差异。这些数据强烈暗示了RSV细支气管炎发病机制中过量的2型和/或缺乏的1型免疫反应。
We examined the in vivo immune response of infants to natural respiratory syncytial virus (RSV) infection through analysis of cytokine levels in nasal lavage fluid and stimulated peripheral blood mononuclear cells. Eighty-eight babies with at least one parent with atopy and asthma were prospectively studied through their first winter. Twenty-eight infants had an upper respiratory tract infection where RSV was detected, of whom nine developed signs of acute bronchiolitis. Nasal lavage specimens were assayed for interferon-gamma, interleukin (IL)-4, IL-10, and IL-12 and the RSV load determined by quantitative polymerase chain reaction. Messenger RNA (mRNA) was extracted from stimulated peripheral blood mononuclear cells and interferon-gamma, IL-4, IL-12, and IL-18 mRNA levels determined by polymerase chain reaction. Cytokine profiles were analyzed in relation to clinical outcome. The IL-4/interferon-gamma ratio for infants with acute bronchiolitis was elevated in nasal lavage fluid on both Days 1-2 (p = 0.014) and Days 5-7 (p = 0.001) of the illness compared with infants with upper respiratory tract infection alone. Those with acute bronchiolitis demonstrated a higher IL-10/IL-12 ratio (p = 0.0015) on Days 1-2. IL-18 mRNA levels were reduced (p = 0.019) and the IL-4/interferon-gamma ratio elevated (p = 0.01) in stimulated peripheral blood mononuclear cells from infants with acute bronchiolitis. There was no difference in initial RSV load. These data strongly implicate excess type 2 and/or deficient type 1 immune responses in the pathogenesis of RSV bronchiolitis.