Innate Immune Dysfunction is Associated with Enhanced Disease Severity In Infants with Severe Respiratory Syncytial Virus Bronchiolitis
Innate Immune Dysfunction is Associated with Enhanced Disease Severity In Infants with Severe Respiratory Syncytial Virus Bronchiolitis
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DOI：
10.1093/infdis/jis719
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发表时间：
2013-02-15
影响因子：
6.4
通讯作者：
Arvin, Ann M.
中科院分区：
文献类型：
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作者：
Gans, Hayley A.;Yasukawa, Linda L.;Arvin, Ann M.
背景。大多数需要入住儿科重症监护病房 (PICU) 的呼吸道合胞病毒 (RSV) 细支气管炎患者没有严重疾病的危险因素。我们试图研究血清细胞因子浓度、先天免疫反应性和 RSV 疾病严重程度之间的关系。方法。纳入既往健康的患有 RSV 细支气管炎的婴儿（中位年龄 2.6 个月）（PICU，n = 20；地板，n = 46）和健康匹配对照（n = 14），并在入院 24 小时内采集血样以测量血浆肿瘤坏死因子 α (TNF-α)、白细胞介素 6 (IL-6)、白细胞介素 8 (IL-8) 和 白细胞介素 10 (IL-10) 浓度和全血脂多糖刺激的细胞因子产生能力。结果。 PICU 患者和楼层患者的血浆 IL-6、IL-8 和 IL-10 浓度相当，但高于健康对照 (P < .05)。相反，与楼层患者和健康对照相比，PICU 中 TNF-α、IL-6 和 IL-8 的产生能力显着下降。在调整后的分析中，只有 TNF-α 和 IL-8 产生能力受损与更长的住院时间 (P = .035) 和更大的疾病严重程度评分 (P = .001) 相关。结论。患有严重 RSV 细支气管炎的婴儿血浆细胞因子浓度升高，但先天免疫细胞因子产生能力受损，这预示着更糟糕的疾病结果。对患有 RSV 下呼吸道感染的其他健康婴儿进行免疫监测有助于识别住院时有患严重疾病风险的患者。
Background. Most patients with respiratory syncytial virus (RSV) bronchiolitis requiring admission to the pediatric intensive care unit (PICU) have no risk factors for severe disease. We sought to investigate the relationship between serum cytokine concentrations, innate immune responsiveness, and RSV disease severity.Methods. Previously healthy infants (median age, 2.6 months) with RSV bronchiolitis (PICU, n = 20; floor, n = 46) and healthy matched controls (n = 14) were enrolled, and blood samples were obtained within 24 hours of admission to measure plasma tumor necrosis factor alpha (TNF-alpha), interleukin 6 (IL-6), interleukin 8 (IL-8), and interleukin 10 (IL-10) concentrations and, whole blood lipopolysaccharide-stimulated cytokine production capacity.Results. Plasma IL-6, IL-8, and IL-10 concentrations were comparable between PICU and floor patients, but higher than in healthy controls (P < .05). In contrast, TNF-alpha, IL-6, and IL-8 production capacity was significantly decreased in PICU compared with both floor patients and healthy controls. In adjusted analyses, only impaired TNF-alpha and IL-8 production capacity were associated with longer length of stay (P = .035) and greater disease severity scores (P = .001).Conclusions. Infants with severe RSV bronchiolitis had increased plasma cytokine concentrations and yet impaired innate immunity cytokine production capacity, which predicted worse disease outcomes. Immune monitoring of otherwise healthy infants with RSV lower respiratory tract infection could help identify patients at risk for severe disease at the time of hospitalization.