Ramos Gerardo, Nghiem Dat X, Walterscheid Jeffrey P, Ullrich Stephen E
Department of Immunology, The University of Texas, Houston, Texas, 77030
Toxicol Appl Pharmacol. 2002 Apr 15;180(2):136-44. doi: 10.1006/taap.2002.9380.
Applying military jet fuel (JP-8) to the skin of mice activates systemic immune suppression. In all of our previous experiments, JP-8 was applied to immunologically naïve mice. The effect of jet fuels on established immune reactions, such as immunological memory, is unknown. The focus of the experiments presented here was to test the hypothesis that jet fuel exposure [both JP-8 and commercial jet fuel (Jet-A)] suppresses established immune reactions. Mice were immunized with the opportunistic fungal pathogen Candida albicans and, at different times after immunization (10 to 30 days), various doses of undiluted JP-8 or Jet-A were applied to their skin. Both the elicitation of delayed-type hypersensitivity (DTH) (mice challenged 10 days after immunization) and immunological memory (mice challenged 30 days after immunization) were significantly suppressed in a dose-dependent manner. Dermal exposure to either multiple small doses (50 microl over 4 days) or a single large dose (approximately 200-300 microl) of JP-8 and/or Jet-A suppressed DTH to C. albicans. The mechanism by which dermal application of JP-8 and Jet-A suppresses immunological memory involves the release of immune biologic response modifiers. Blocking the production of prostaglandin E(2) by a selective cyclooxygenase-2 inhibitor (SC 236) significantly reversed jet fuel-induced suppression of immunologic memory. These findings indicate, for the first time, that dermal exposure to commercial jet fuel (Jet-A) suppresses the immune response. In addition, the data reported here expand on previous findings by suggesting that jet fuel exposure may depress the protective effect of prior vaccination.
将军用喷气燃料(JP - 8)涂抹于小鼠皮肤会激活全身免疫抑制。在我们之前所有的实验中,JP - 8均应用于免疫初免的小鼠。喷气燃料对已建立的免疫反应(如免疫记忆)的影响尚不清楚。本文所呈现实验的重点是检验喷气燃料暴露(JP - 8和商用喷气燃料Jet - A)会抑制已建立的免疫反应这一假说。用机会性真菌病原体白色念珠菌对小鼠进行免疫,在免疫后的不同时间点(10至30天),将不同剂量的未稀释JP - 8或Jet - A涂抹于它们的皮肤上。迟发型超敏反应(DTH)的激发(免疫后10天对小鼠进行攻击)和免疫记忆(免疫后30天对小鼠进行攻击)均以剂量依赖的方式受到显著抑制。皮肤暴露于多个小剂量(4天内50微升)或单个大剂量(约200 - 300微升)的JP - 8和/或Jet - A会抑制对白色念珠菌的DTH。皮肤涂抹JP - 8和Jet - A抑制免疫记忆的机制涉及免疫生物反应调节剂的释放。通过选择性环氧化酶 - 2抑制剂(SC 236)阻断前列腺素E(2)的产生可显著逆转喷气燃料诱导的免疫记忆抑制。这些发现首次表明,皮肤暴露于商用喷气燃料(Jet - A)会抑制免疫反应。此外,本文报道的数据扩展了先前的研究结果,表明喷气燃料暴露可能会削弱先前疫苗接种的保护作用。