Legg Julian P, Hussain Imran R, Warner Jill A, Johnston Sebastian L, Warner John O
Department of Child Health, Infection, Inflammation and Repair Division, University of Southampton, Southampton SO16 6YD, UK.
Am J Respir Crit Care Med. 2003 Sep 15;168(6):633-9. doi: 10.1164/rccm.200210-1148OC. Epub 2003 May 28.
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.
我们通过分析鼻洗液和刺激外周血单个核细胞中的细胞因子水平，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。对88名父母中至少有一方患有特应性疾病和哮喘的婴儿进行了前瞻性研究，观察他们度过的第一个冬季。28名婴儿发生了上呼吸道感染并检测出RSV，其中9名出现了急性细支气管炎的症状。对鼻洗液标本检测干扰素-γ、白细胞介素（IL）-4、IL-10和IL-12，并通过定量聚合酶链反应测定RSV载量。从刺激的外周血单个核细胞中提取信使核糖核酸（mRNA），并通过聚合酶链反应测定干扰素-γ、IL-4、IL-12和IL-18的mRNA水平。分析细胞因子谱与临床结局的关系。与仅患有上呼吸道感染的婴儿相比，急性细支气管炎婴儿在疾病第1 - 2天（p = 0.014）和第5 - 7天（p = 0.001）的鼻洗液中IL-4/干扰素-γ比值升高。患有急性细支气管炎的婴儿在第1 - 2天IL-10/IL-12比值更高（p = 0.0015）。急性细支气管炎婴儿刺激外周血单个核细胞中的IL-18 mRNA水平降低（p = 0.019），IL-4/干扰素-γ比值升高（p = 0.01）。初始RSV载量无差异。这些数据强烈提示2型免疫反应过度和/或1型免疫反应不足在RSV细支气管炎发病机制中起作用。
