Negherbon Jesse P, Romero Karina, Williams D'Ann L, Guerrero-Preston Rafael E, Hartung Thomas, Scott Alan L, Breysse Patrick N, Checkley William, Hansel Nadia N
Department of Environmental Health Sciences, Bloomberg School of Public Health, The Johns Hopkins University, BaltimoreMD, USA.
Asociación Benéfica PrismaLima, Perú.
Front Pharmacol. 2017 Mar 30;8:157. doi: 10.3389/fphar.2017.00157. eCollection 2017.
This study sought to investigate if acute phase immune responses of whole blood from Peruvian children with controlled and uncontrolled asthma differed from children without asthma, following exposure to traffic-related particulate matter (TRPM). TRPM, including particulate matter from diesel combustion, has been shown to stimulate acute airway inflammation in individuals with and without asthma. For this study, a whole blood assay (WBA) was used to test peripheral whole blood samples from 27 children with asthma, and 12 without asthma. Participant blood samples were stimulated, , for 24-h with an aqueous extract of TRPM that was collected near study area highways in Lima, Peru. All participant blood samples were tested against the same TRPM extract, in addition to purified bacterial endotoxin and pyrogen-free water, which served as positive and negative WBA controls, respectively. The innate and adaptive cytokine responses were evaluated in cell-free supernatants of the whole blood incubations. Comparatively similar levels were recorded for nine out of the 10 cytokines measured [e.g., - Interleukin (IL)-1β, IL-6, IL-10], regardless of study participant asthma status. However, IL-8 levels in TRPM-stimulated blood from children with uncontrolled asthma were diminished, compared to subjects without asthma (633 pg/ml vs. 1,023 pg/ml, respectively; < 0.01); IL-8 responses for subjects with controlled asthma were also reduced, but to a lesser degree (799 pg/ml vs. 1,023 pg/ml, respectively; = 0.10). These relationships were present before, and after, adjusting for age, sex, obesity/overweight status, C-reactive protein levels, and residential proximity to the study area's major roadway. For tests conducted with endotoxin, there were no discernible differences in cytokine response between groups, for all cytokines measured. The WBA testing conducted for this study highlighted the capacity of the TRPM extract to potently elicit the release of IL-8 from the human whole blood system. Although the small sample size of the study limits the capacity to draw definitive conclusions, the IL-8 responses suggest that that asthma control may be associated with the regulation of a key mediator in neutrophil chemotaxis, at a systemic level, following exposure to PM derived from traffic-related sources.
本研究旨在调查秘鲁患可控哮喘和不可控哮喘儿童的全血急性期免疫反应,在暴露于交通相关颗粒物(TRPM)后,是否与无哮喘儿童存在差异。TRPM,包括柴油燃烧产生的颗粒物,已被证明会刺激有哮喘和无哮喘个体的急性气道炎症。在本研究中,采用全血检测法(WBA)检测了27名哮喘儿童和12名无哮喘儿童的外周全血样本。参与者的血样用从秘鲁利马研究区域高速公路附近采集的TRPM水提取物刺激24小时。除了分别作为WBA阳性和阴性对照的纯化细菌内毒素和无热原水外,所有参与者的血样都用相同的TRPM提取物进行检测。在全血孵育的无细胞上清液中评估先天性和适应性细胞因子反应。在所测量的10种细胞因子中,有9种记录到相对相似的水平[例如,白细胞介素(IL)-1β、IL-6、IL-10],与研究参与者的哮喘状态无关。然而,与无哮喘受试者相比,不可控哮喘儿童的TRPM刺激血液中的IL-8水平降低(分别为633 pg/ml和1,023 pg/ml;P<0.01);可控哮喘受试者的IL-8反应也降低,但程度较轻(分别为799 pg/ml和1,023 pg/ml;P = 0.10)。在调整年龄、性别、肥胖/超重状态、C反应蛋白水平以及与研究区域主要道路的居住距离后,这些关系依然存在。对于用内毒素进行的检测,在所测量的所有细胞因子中,各组之间的细胞因子反应没有明显差异。本研究进行的WBA检测突出了TRPM提取物从人类全血系统中有效诱导IL-8释放的能力。尽管研究样本量小限制了得出明确结论的能力,但IL-8反应表明,在暴露于交通相关来源的颗粒物后,哮喘控制可能与全身水平上中性粒细胞趋化作用关键介质的调节有关。