Stiegel Matthew A, Pleil Joachim D, Sobus Jon R, Stevens Tina, Madden Michael C
a Duke University Medical Center , Department of Occupational and Environmental Safety , Durham , NC , US.
b United States Environmental Protection Agency, National Exposure Research Lab , Exposure Methods and Measurement Division , Research Triangle Park , NC , US.
J Toxicol Environ Health A. 2017;80(9):485-501. doi: 10.1080/15287394.2017.1330578. Epub 2017 Jul 11.
Human biomonitoring is an indispensable tool for evaluating the systemic effects derived from external stressors including environmental pollutants, chemicals from consumer products, and pharmaceuticals. The aim of this study was to explore consequences of environmental exposures to diesel exhaust (DE) and ozone (O) and ultimately to interpret these parameters from the perspective of in vitro to in vivo extrapolation. In particular, the objective was to use cytokine expression at the cellular level as a biomarker for physiological systemic responses such as blood pressure and lung function at the systemic level. The values obtained could ultimately link in vivo behavior to simpler in vitro experiments where cytokines are a measured parameter. Human exposures to combinations of DE and O and the response correlations between forced exhaled volume in 1 second (FEV), forced vital capacity (FVC), systolic and diastolic blood pressure (SBP and DBP, respectively), and 10 inflammatory cytokines in blood (interleukins 1β, 2, 4, 5, 8, 10, 12p70 and 13, IFN-γ, and TNF-α) were determined in 15 healthy human volunteers. Results across all exposures revealed that certain individuals displayed greater inflammatory responses compared to the group and, generally, there was more between-person variation in the responses. Evidence indicates that individuals are more stable within themselves and are more likely to exhibit responses independent of one another. Data suggest that in vitro findings may ultimately be implemented to elucidate underlying adverse outcome pathways (AOP) for linking high-throughput toxicity tests to physiological in vivo responses. Further, this investigation supports assessing subjects based upon individual responses as a complement to standard longitudinal (pre vs. post) intervention grouping strategies. Ultimately, it may become possible to predict a physiological (systemic) response based upon cellular-level (in vitro) observations.
人体生物监测是评估外部应激源（包括环境污染物、消费品中的化学物质和药物）所产生的全身效应的不可或缺的工具。本研究的目的是探讨环境暴露于柴油废气（DE）和臭氧（O）的后果，并最终从体外到体内外推的角度解释这些参数。具体而言，目标是将细胞水平的细胞因子表达用作全身水平生理全身反应（如血压和肺功能）的生物标志物。获得的值最终可以将体内行为与更简单的体外实验联系起来，在体外实验中细胞因子是一个测量参数。在15名健康人类志愿者中测定了人体暴露于DE和O的组合以及1秒用力呼气量（FEV）、用力肺活量（FVC）、收缩压和舒张压（分别为SBP和DBP）与血液中10种炎性细胞因子（白细胞介素1β、2、4、5、8、10、12p70和13、IFN-γ和TNF-α）之间的反应相关性。所有暴露的结果显示，与该组相比，某些个体表现出更大的炎症反应，并且一般来说，反应中的个体间差异更大。有证据表明个体自身更稳定，并且更有可能表现出相互独立的反应。数据表明，体外研究结果最终可能用于阐明潜在的不良结局途径（AOP），以将高通量毒性试验与体内生理反应联系起来。此外，本研究支持根据个体反应评估受试者，作为对标准纵向（干预前与干预后）分组策略的补充。最终，基于细胞水平（体外）观察来预测生理（全身）反应可能成为可能。
