Dermal Exposure to Jet Fuel suppresses Delayed Type Hypersensitivity: A Critical Role for Aromatic Hydrocarbons.
Department of Immunology and The Center for Cancer Immunology Research, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030.
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, prostaglandin E(2), and interleukin-10, and 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 up-regulate the expression of epidermal cyclooxygenase-2 nor does it induce immune suppression. Adding back a cocktail of 7 of the most prevalent aromatic hydrocarbons found in jet fuel (benzene, toluene, ethylbenzene, xylene, 1,2,4-trimethlybenzene, cyclohexylbenzene and dimethylnaphthalene) to S-8 up-regulated epidermal cyclooxygenase-2 expression and suppressed a delayed-type hypersensitivity (DTH) reaction. Injecting platelet activating factor 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 up-regulation of cyclooxygenase-2, and the production of immune regulatory factors and cytokines.
PMID: 17890764 [PubMed - as supplied by publisher]