Inflammatory Cytokines and White Blood Cell Counts Response to Environmental Levels of Diesel Exhaust and Ozone Inhalation Exposures.
Inflammatory Cytokines and White Blood Cell Counts Response to Environmental Levels of Diesel Exhaust and Ozone Inhalation Exposures.
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DOI：
10.1371/journal.pone.0152458
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Madden MC
中科院分区：
文献类型：
--
作者：
Stiegel MA;Pleil JD;Sobus JR;Madden MC
对城市吸入暴露于柴油机废气（DE）和臭氧（O3）的流行病学观察表明，人类存在临床前心肺反应。确定启动这些健康生物指标的关键生物机制是困难的，因为环境暴露的时间和人与人之间的差异。以前，环境控制的人体暴露室已被用来研究DE和O3剂量-反应模式分开，但共同曝光的调查还没有在受控条件下进行。由于混合物是一个更现实的暴露场景，为广大市民，在这项研究中，我们调查的城市水平的DE暴露（300 μg/m3），O3（0.3 ppm），DE + O3共同暴露，和先天免疫系统反应的关系。研究了15名健康志愿者在受控暴露于DE、O3和DE+O3后10种炎性细胞因子（白细胞介素1β、2、4、5、8、10、12 p70和13、IFN-γ和TNF-α）和3种白色血细胞类型（淋巴细胞、单核细胞和中性粒细胞）计数的变化。结果表明，仅柴油和仅臭氧暴露的细胞因子反应很小，并且这两种暴露的组合存在更复杂（可能是协同的）关系，其中IL-5，IL-12 p70，IFN-γ和TNF-α的抑制持续长达22小时。DE + O3暴露后，白色血细胞分类计数显示单核细胞和淋巴细胞显著减少，中性粒细胞显著增加;淋巴细胞和中性粒细胞变化也持续至少22小时。由于人体研究必须在严格的环境水平安全协议下进行，这些影响是微妙的，通常只有通过详细的统计分析才能看到。这项研究表明，所观察到的环境暴露和心肺效应之间的关联可能是由炎症反应机制介导的。
Epidemiological observations of urban inhalation exposures to diesel exhaust (DE) and ozone (O3) have shown pre-clinical cardiopulmonary responses in humans. Identifying the key biological mechanisms that initiate these health bioindicators is difficult due to variability in environmental exposure in time and from person to person. Previously, environmentally controlled human exposure chambers have been used to study DE and O3 dose-response patterns separately, but investigation of co-exposures has not been performed under controlled conditions. Because a mixture is a more realistic exposure scenario for the general public, in this study we investigate the relationships of urban levels of urban-level DE exposure (300 μg/m3), O3 (0.3 ppm), DE + O3 co-exposure, and innate immune system responses. Fifteen healthy human volunteers were studied for changes in ten inflammatory cytokines (interleukins 1β, 2, 4, 5, 8, 10, 12p70 and 13, IFN-γ, and TNF-α) and counts of three white blood cell types (lymphocytes, monocytes, and neutrophils) following controlled exposures to DE, O3, and DE+O3. The results show subtle cytokines responses to the diesel-only and ozone-only exposures, and that a more complex (possibly synergistic) relationship exists in the combination of these two exposures with suppression of IL-5, IL-12p70, IFN-γ, and TNF-α that persists up to 22-hours for IFN-γ and TNF-α. The white blood cell differential counts showed significant monocyte and lymphocyte decreases and neutrophil increases following the DE + O3 exposure; lymphocytes and neutrophils changes also persist for at least 22-hours. Because human studies must be conducted under strict safety protocols at environmental levels, these effects are subtle and are generally only seen with detailed statistical analysis. This study indicates that the observed associations between environmental exposures and cardiopulmonary effects are possibly mediated by inflammatory response mechanisms.