Mechanisms involved in the immunotoxicity induced by dermal application ofJP-8 jet fuel

Dermal application of JP-8 jet fuel induces immune suppression. Classic del ayed-type hypersensitivity as well as the induction of contact hypersensiti vity to allergens applied to the shaved skin of JP-8-treated mice is suppre ssed. In addition, the ability of T cells isolated from JP-8-treated mice t o proliferate in vitro is suppressed. Here we focused on further characteri zing the immunotoxicity induced by JP-8 exposure and determining the mechan ism involved. Suppression of T-cell proliferation was first noted 3 to 4 da ys after a single JP-8 treatment and lasted for approximately 3 weeks, at w hich time T-cell proliferation returned to normal. Cellular immune reaction s appear to be more susceptible to the immunosuppressive effects of JP-8, a s antibody production in JP-8-treated mice was identical to that found in n ormal controls. The mechanism through which dermal application of JP-8 supp resses cell-mediated immune reactions appears to be via the release of immu ne biological-response modifiers. Blocking the production of prostaglandin E-2 with a selective cyclooxygenase-2 inhibitor abrogated JP-8-induced immu ne suppression. Neutralizing the activity of interleukin-10 with a highly s pecific monoclonal antibody also blocked JP-8-induced immune suppression. F urthermore, injecting JP-8-treated mice with recombinant interleukin-12, a cytokine that drives cell-mediated immune reactions in vivo, overcame the i mmunotoxic effects of JP-8 and restored immune function. These data indicat e that immune suppressive cytokines, presumably produced by JP-8-treated ep idermal cells, are responsible for immune suppression in JP-8-treated mice and that blocking and/or neutralizing their production in vivo overcomes th e immunotoxic effects of JP-8.