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木柴烟雾暴露以性别特异性方式改变人类对病毒感染的炎症反应。一项随机、安慰剂对照研究。

Wood Smoke Exposure Alters Human Inflammatory Responses to Viral Infection in a Sex-Specific Manner. A Randomized, Placebo-controlled Study.

机构信息

1 Curriculum in Toxicology & Environmental Medicine.

2 Department of Environmental Sciences and Engineering, Gillings School of Global Public Health.

出版信息

Am J Respir Crit Care Med. 2019 Apr 15;199(8):996-1007. doi: 10.1164/rccm.201807-1287OC.

DOI:10.1164/rccm.201807-1287OC
PMID:30360637
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6467301/
Abstract

RATIONALE

Exposure to particulates from burning biomass is an increasing global health issue. Burning biomass, including wood smoke, is associated with increased lower respiratory infections.

OBJECTIVES

To determine whether acute exposure to wood smoke modifies nasal inflammatory responses to influenza.

METHODS

Healthy young adults (n = 39) were randomized to a 2-hour controlled chamber exposure to wood smoke, where exposure levels were controlled to particulate number (wood smoke particles [WSP]; 500 μg/cm) or filtered air, followed by nasal inoculation with a vaccine dose of live attenuated influenza virus (LAIV). Nasal lavage was performed before exposure (Day 0) and on Days 1 and 2 after exposure. Nasal lavage fluid cells were analyzed for inflammatory gene expression profiles, and cell-free fluid was assayed for cytokines.

MEASUREMENTS AND MAIN RESULTS

Only IP-10 protein levels were affected, suppressed, by WSP exposure in aggregate analysis. Subsequent analysis indicated an exposure × sex interaction, prompting additional analyses of WSP- and LAIV-induced changes in males and females. Inflammation-related gene expression profiles differed between the sexes, at baseline (males greater than females), after LAIV inoculation (females greater than males), and after WSP exposure (increase in males and decrease in females), demonstrating that WSP- and LAIV-induced changes in antiviral defense responses in the nasal mucosa occur in a sex-specific manner.

CONCLUSIONS

WSP exposure resulted in minimal modification of LAIV-induced responses in aggregate analysis. In contrast, analyzing WSP-induced modification of LAIV responses in the sexes separately unmasked sex-specific differences in response to exposure. These data highlight the need for additional studies to understand sex-specific pollutant-induced effects. Clinical trial registered with www.clinicaltrials.gov (NCT02183753).

摘要

背景

燃烧生物质(包括木柴燃烧)所产生的颗粒物暴露是一个日益严重的全球健康问题,与下呼吸道感染的增加有关。

目的

确定急性暴露于木柴烟雾是否会改变鼻腔对流感的炎症反应。

方法

将 39 名健康的年轻成年人随机分为两组,分别在 2 小时内受控暴露于木柴烟雾或过滤空气中,然后用减毒活流感疫苗(LAIV)进行鼻腔接种。在暴露前(第 0 天)以及暴露后第 1 天和第 2 天进行鼻冲洗。分析鼻冲洗液中的细胞炎症基因表达谱,并检测无细胞鼻冲洗液中的细胞因子。

测量和主要结果

仅在综合分析中,木柴烟雾暴露会抑制 IP-10 蛋白水平。随后的分析表明,暴露与性别存在相互作用,促使对男性和女性进行木柴烟雾和 LAIV 诱导变化的进一步分析。在基线(男性大于女性)、LAIV 接种后(女性大于男性)和木柴烟雾暴露后(男性增加和女性减少),炎症相关基因表达谱在性别之间存在差异,这表明木柴烟雾和 LAIV 诱导的鼻腔黏膜抗病毒防御反应变化以性别特异性的方式发生。

结论

在综合分析中,木柴烟雾暴露对 LAIV 诱导的反应仅有微小的修饰作用。相比之下,分别分析木柴烟雾对 LAIV 反应的修饰作用揭示了对暴露的反应存在性别特异性差异。这些数据强调了需要进一步研究以了解性别特异性污染物诱导的影响。临床试验在 www.clinicaltrials.gov 上注册(NCT02183753)。

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