Meadows Jacqueline R, Parker Chevonne, Gilbert Kathleen M, Blossom Sarah J, DeWitt Jamie C
a Department of Pharmacology and Toxicology , Brody School of Medicine, East Carolina University Greenville , NC , USA.
b Department of Microbiology and Immunology , UAMS College of Medicine, Arkansas Children's Research Institute , Little Rock , AR , USA.
J Immunotoxicol. 2017 Dec;14(1):95-102. doi: 10.1080/1547691X.2017.1305021.
Trichloroethylene (TCE) is a widespread environmental contaminant associated with developmental immunotoxicity and neurotoxicity. Previous studies have shown that MRL mice exposed to TCE from gestation through early-life demonstrate robust increases in inflammatory markers in peripheral CD4 T-cells, as well as glutathione depletion and increased oxidative stress in cerebellum-associated with alterations in behavior. Since increased oxidative stress is associated with neuroinflammation, we hypothesized that neuroinflammatory markers could be altered relative to unexposed mice. MRL mice were given 0.5 mg/ml of TCE in vehicle or vehicle (water with 1% Alkamuls EL-620) from conception through early adulthood via drinking water to dams and then directly to post-weaning offspring. Animals were euthanized at 49 days of age and levels of pro- and anti-inflammatory cytokines, density of T-cell staining, and micro-glial morphology were evaluated in brains to begin to ascertain a neuroinflammatory profile. Levels of IL-6 were decreased in female animals and while not statistically significant, and levels of IL-10 were higher in brains of exposed male and female animals. Supportive of this observation, although not statistically significant, the number of ameboid microglia was higher in exposed relative to unexposed animals. This overall profile suggests the emergence of an anti-inflammatory/neuroprotective phenotype in exposed animals, possibly as a compensatory response to neuroinflammation that is known to be induced by developmental exposure to TCE.
三氯乙烯（TCE）是一种广泛存在的环境污染物，与发育性免疫毒性和神经毒性有关。先前的研究表明，从妊娠期到生命早期暴露于TCE的MRL小鼠外周CD4 T细胞中的炎症标志物显著增加，同时小脑谷胱甘肽耗竭和氧化应激增加，这与行为改变有关。由于氧化应激增加与神经炎症有关，我们推测与未暴露小鼠相比，神经炎症标志物可能会发生改变。从受孕到成年早期，通过给母鼠饮用含0.5 mg/ml TCE的溶剂或溶剂（含1% Alkamuls EL-620的水），然后直接给断奶后的后代饮用。在动物49日龄时实施安乐死，评估大脑中促炎和抗炎细胞因子水平、T细胞染色密度和小胶质细胞形态，以确定神经炎症特征。雌性动物中白细胞介素-6（IL-6）水平降低，虽然无统计学意义，但暴露的雄性和雌性动物大脑中白细胞介素-10（IL-10）水平较高。支持这一观察结果的是，虽然无统计学意义，但与未暴露动物相比，暴露动物中阿米巴样小胶质细胞的数量更多。这一总体特征表明，暴露动物中出现了抗炎/神经保护表型，这可能是对已知由发育性暴露于TCE诱导的神经炎症的一种代偿反应。
