McNamara Paul S, Flanagan Brian F, Baldwin Lisa M, Newland Paul, Hart C Anthony, Smyth Rosalind L
Department of Child Health, University of Liverpool, Institute of Child Health, Alder Hey Children's Hospital, Liverpool, UK.
Lancet. 2004 Mar 27;363(9414):1031-7. doi: 10.1016/S0140-6736(04)15838-8.
Respiratory syncytial virus (RSV) bronchiolitis is the most prevalent acute wheezing disorder in infants and is associated with recurrent wheeze and asthma in childhood. Interleukin 9, a type 2 cytokine has been proposed as a key cytokine in susceptibility to asthma. We aimed to investigate whether interleukin 9 was produced in the lungs of infants with severe RSV disease and if found, from which cells it originated.
We did 150 non-bronchoscopic bronchoalveolar lavages during the course of ventilation in 24 term infants and 21 preterm infants ventilated for RSV bronchiolitis. We also did 10 bronchoalveolar lavages on the day of intubation in 10 control infants ventilated for non-respiratory causes. We measured pulmonary interleukin 9 mRNA and protein in samples from all groups. We used immunostaining to identify the cells that produce interleukin 9.
Interleukin 9 mRNA expression, which persisted over the course of ventilation, was noted in all infants with bronchiolitis. Three of the control group also showed interleukin 9 mRNA expression. Median interleukin 9 protein concentration on day 1 (1.9 microg/L [range 0.1-36.2]) was significantly greater in term infants with bronchiolitis than either preterm infants (0.4 microg/L [0.1-2.9]; p<0.05) or the control group (0.7 microg/L [0.4-2.5]; p<0.05). There was a trend for interleukin 9 protein concentrations in term, but not preterm infants to decrease over time. Immunostained cell smears showed that most interleukin 9 expression in bronchoalveolar lavage was by neutrophils.
In term infants with RSV bronchiolitis, we noted large amounts of interleukin 9 mRNA and interleukin 9 protein. Neutrophils seem to be the main source of this type 2 cytokine. Interleukin 9 production by neutrophils may contribute to the pathogenesis of RSV disease. These findings may be relevant to other disease processes in the lung where neutrophils are the predominant inflammatory cell type.
呼吸道合胞病毒（RSV）细支气管炎是婴儿中最常见的急性喘息性疾病，与儿童期反复喘息和哮喘有关。白细胞介素9作为一种2型细胞因子，被认为是哮喘易感性的关键细胞因子。我们旨在研究白细胞介素9是否在患有严重RSV疾病的婴儿肺部产生，若有发现，则确定其起源于何种细胞。
我们在24名足月儿和21名因RSV细支气管炎接受通气治疗的早产儿通气过程中进行了150次非支气管镜下支气管肺泡灌洗。我们还在10名因非呼吸道原因接受通气治疗的对照婴儿插管当天进行了10次支气管肺泡灌洗。我们测量了所有组样本中的肺白细胞介素9 mRNA和蛋白。我们使用免疫染色来识别产生白细胞介素9的细胞。
在所有患有细支气管炎的婴儿中均观察到白细胞介素9 mRNA表达，且在通气过程中持续存在。对照组中有3例也显示出白细胞介素9 mRNA表达。足月儿细支气管炎患儿第1天白细胞介素9蛋白浓度中位数（1.9μg/L[范围0.1 - 36.2]）显著高于早产儿（0.4μg/L[0.1 - 2.9]；p<0.05）或对照组（0.7μg/L[0.4 - 2.5]；p<0.05）。足月儿而非早产儿的白细胞介素9蛋白浓度有随时间下降的趋势。免疫染色细胞涂片显示，支气管肺泡灌洗中大多数白细胞介素9表达来自中性粒细胞。
在患有RSV细支气管炎的足月儿中，我们发现了大量的白细胞介素9 mRNA和白细胞介素9蛋白。中性粒细胞似乎是这种2型细胞因子的主要来源。中性粒细胞产生白细胞介素9可能有助于RSV疾病的发病机制。这些发现可能与肺部以中性粒细胞为主要炎症细胞类型的其他疾病过程相关。
