Journal Article

Mechanisms Involved in the Immunotoxicity Induced by Dermal Application of JP-8 Jet Fuel

Stephen E. Ullrich and Heather J. Lyons

in Toxicological Sciences

Volume 58, issue 2, pages 290-298
Published in print December 2000 | ISSN: 1096-6080
Published online December 2000 | e-ISSN: 1096-0929 | DOI: http://dx.doi.org/10.1093/toxsci/58.2.290
Mechanisms Involved in the Immunotoxicity Induced by Dermal Application of JP-8 Jet Fuel

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Dermal application of JP-8 jet fuel induces immune suppression. Classic delayed-type hypersensitivity as well as the induction of contact hypersensitivity to allergens applied to the shaved skin of JP-8-treated mice is suppressed. In addition, the ability of T cells isolated from JP-8-treated mice to proliferate in vitro is suppressed. Here we focused on further characterizing the immunotoxicity induced by JP-8 exposure and determining the mechanism involved. Suppression of T-cell proliferation was first noted 3 to 4 days after a single JP-8 treatment and lasted for approximately 3 weeks, at which time T-cell proliferation returned to normal. Cellular immune reactions appear to be more susceptible to the immunosuppressive effects of JP-8, as antibody production in JP-8-treated mice was identical to that found in normal controls. The mechanism through which dermal application of JP-8 suppresses cell-mediated immune reactions appears to be via the release of immune biological-response modifiers. Blocking the production of prostaglandin E2 with a selective cyclooxygenase-2 inhibitor abrogated JP-8-induced immune suppression. Neutralizing the activity of interleukin-10 with a highly specific monoclonal antibody also blocked JP-8-induced immune suppression. Furthermore, injecting JP-8-treated mice with recombinant interleukin-12, a cytokine that drives cell-mediated immune reactions in vivo, overcame the immunotoxic effects of JP-8 and restored immune function. These data indicate that immune suppressive cytokines, presumably produced by JP-8-treated epidermal cells, are responsible for immune suppression in JP-8-treated mice and that blocking and/or neutralizing their production in vivo overcomes the immunotoxic effects of JP-8.

Keywords: jet fuel; JP-8; immune suppression; prostaglandin E2; interleukin-10; interleukin-12; cytokines; immunotoxicity

Journal Article.  7148 words.  Illustrated.

Subjects: Medical Toxicology ; Toxicology (Non-medical)

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