Burchiel Scott W, Lauer Fredine T, MacKenzie Debra, McClain Shea, Kuehl Philip J, McDonald Jacob D, Harrod Kevin S
a Department of Pharmaceutical Sciences , College of Pharmacy, The University of New Mexico , Albuquerque , NM , USA .
b Lovelace Respiratory Research Institute , Albuquerque , NM , USA , and.
Inhal Toxicol. 2016;28(2):61-70. doi: 10.3109/08958378.2015.1136714.
Previous studies have shown that complex mixtures containing particulate matter (PM) and polycyclic aromatic hydrocarbons (PAHs) produce systemic immunotoxicity in animal models following inhalation exposures. While we and others have shown that emissions associated with hardwood smoke (HWS), cigarette smoke and diesel exhaust can suppress the immune systems of animals in vitro and in vivo, there have been few immune function studies on human peripheral blood mononuclear cells (HPBMC) following exposure of humans to HWS. Our work shows that T cells are an important targets of PM and PAH immunotoxicity. These studies were conducted on HPBMC from 14 human volunteers receiving four 2 h nightly exposures to clean air or HWS at a concentration of 500 ug/m(3). We measured anti-CD3/anti-CD28 stimulated T-cell proliferation and HPBMC cytokine production in cell supernatants, including interleukin 1β (IL-1β), tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), interleukin 8 (IL-8), TH1 cytokines γIFN and IL-2, TH2 cytokine IL-4, Th17 cytokine interleukin 17A (IL-17A) and interleukin 10 (IL-10). We analyzed results using analysis of variance (ANOVA), t-tests and Pearson correlation. Results showed that there was significant variation in the amount of T-cell proliferation observed following polyclonal activation with anti-CD3/anti-CD28 antibodies in both the air and HWS-exposed groups. There was not a significant effect of HWS on T-cell proliferation. However, we did find a strong relationship between the presence of proinflammatory cytokines (IL-1β, TNF-α, IL-6, but not IL-8) and the amount of T-cell proliferation seen in individual donors, demonstrating that brief exposures of humans to HWS can produce changes in systemic immunity that is associated with proinflammatory cytokines.
先前的研究表明，含有颗粒物（PM）和多环芳烃（PAH）的复杂混合物在吸入暴露后会在动物模型中产生全身免疫毒性。虽然我们和其他人已经表明，与硬木烟雾（HWS）、香烟烟雾和柴油废气相关的排放物可在体外和体内抑制动物的免疫系统，但在人类暴露于HWS后，针对人类外周血单核细胞（HPBMC）的免疫功能研究却很少。我们的研究表明，T细胞是PM和PAH免疫毒性的重要靶点。这些研究是针对14名人类志愿者的HPBMC进行的，他们每晚接受4次2小时的清洁空气或浓度为500 μg/m³的HWS暴露。我们测量了抗CD3/抗CD28刺激的T细胞增殖以及细胞上清液中HPBMC细胞因子的产生，包括白细胞介素1β（IL-1β）、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）、TH1细胞因子γ干扰素和IL-2、TH2细胞因子IL-4、Th17细胞因子白细胞介素17A（IL-17A）和白细胞介素10（IL-10）。我们使用方差分析（ANOVA）、t检验和Pearson相关性分析结果。结果表明，在空气组和HWS暴露组中，用抗CD3/抗CD28抗体进行多克隆激活后观察到的T细胞增殖量存在显著差异。HWS对T细胞增殖没有显著影响。然而，我们确实发现促炎细胞因子（IL-1β、TNF-α、IL-6，但不包括IL-8）的存在与个体供体中观察到的T细胞增殖量之间存在密切关系，这表明人类短暂暴露于HWS可导致与促炎细胞因子相关的全身免疫变化。
