Ramos Gerardo, Limon-Flores Alberto Yairh, Ullrich Stephen E
Department of Immunology and The Center for Cancer Immunology Research, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Toxicol Sci. 2007 Dec;100(2):415-22. doi: 10.1093/toxsci/kfm247. Epub 2007 Sep 22.
Dermal exposure to military (JP-8) and/or commercial (Jet-A) jet fuel suppresses cell-mediated immune reactions. Immune regulatory cytokines and biological modifiers, including platelet activating factor (PAF), prostaglandin E(2), and interleukin-10, have been implicated in the pathway of events leading to immune suppression. It is estimated that approximately 260 different hydrocarbons are found in jet fuel, and the exact identity of the active immunotoxic agent(s) is unknown. The recent availability of synthetic jet fuel (S-8), which is refined from natural gas, and is devoid of aromatic hydrocarbons, made it feasible to design experiments to address this problem. Here we tested the hypothesis that the aromatic hydrocarbons present in jet fuel are responsible for immune suppression. We report that applying S-8 to the skin of mice does not upregulate the expression of epidermal cyclooxygenase-2 (COX-2) nor does it induce immune suppression. Adding back a cocktail of seven of the most prevalent aromatic hydrocarbons found in jet fuel (benzene, toluene, ethylbenzene, xylene, 1,2,4-trimethlybenzene, cyclohexylbenzene, and dimethylnaphthalene) to S-8 upregulated epidermal COX-2 expression and suppressed a delayed-type hypersensitivity (DTH) reaction. Injecting PAF receptor antagonists, or a selective cycloozygenase-2 inhibitor into mice treated with S-8 supplemented with the aromatic cocktail, blocked suppression of DTH, similar to data previously reported using JP-8. These findings identify the aromatic hydrocarbons found in jet fuel as the agents responsible for suppressing DTH, in part by the upregulation of COX-2, and the production of immune regulatory factors and cytokines.
皮肤接触军用（JP - 8）和/或商用（Jet - A）喷气燃料会抑制细胞介导的免疫反应。免疫调节细胞因子和生物调节剂，包括血小板活化因子（PAF）、前列腺素E2和白细胞介素 - 10，被认为参与了导致免疫抑制的一系列事件。据估计，喷气燃料中大约含有260种不同的碳氢化合物，而具有免疫毒性的活性成分的确切身份尚不清楚。最近出现的由天然气提炼而成且不含芳烃的合成喷气燃料（S - 8），使得设计实验来解决这个问题成为可能。在这里，我们测试了喷气燃料中存在的芳烃导致免疫抑制这一假设。我们报告称，将S - 8涂抹于小鼠皮肤上不会上调表皮环氧化酶 - 2（COX - 2）的表达，也不会诱导免疫抑制。向S - 8中添加喷气燃料中七种最常见的芳烃混合物（苯、甲苯、乙苯、二甲苯、1,2,4 - 三甲苯、环己基苯和二甲基萘）会上调表皮COX - 2的表达并抑制迟发型超敏反应（DTH）。向用添加了芳烃混合物的S - 8处理的小鼠体内注射PAF受体拮抗剂或选择性环氧化酶 - 2抑制剂，可阻断DTH的抑制作用，这与之前使用JP - 8报道的数据相似。这些发现表明，喷气燃料中的芳烃是抑制DTH的因素，部分原因是通过上调COX - 2以及产生免疫调节因子和细胞因子。
