Mechanisms involved in the immunotoxicity induced by dermal application of JP-8 jet fuel.
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 E(2) 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.
Ullrich
S E
SE
Department of Immunology-178, The University of Texas, M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030-4009, USA. sullrich@notes.mdacc.tmc.edu
Lyons
H J
HJ
D000279:Administration, Cutaneous; D000818:Animals; D000917:Antibody Formation; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000502:physiology; D005260:Female; D006838:Hydrocarbons / Q000008:administration & dosage / Q000633:toxicity*; D007108:Immune Tolerance / Q000187:drug effects*; D016753:Interleukin-10 / Q000502:physiology; D018664:Interleukin-12 / Q000494:pharmacology; D007648:Kerosene / Q000633:toxicity*; D051379:Mice; D008809:Mice, Inbred C3H; D011994:Recombinant Proteins / Q000494:pharmacology
D016861:Cyclooxygenase Inhibitors; D006838:Hydrocarbons; C098607:JP8 aviation fuel; D007648:Kerosene; D011994:Recombinant Proteins; D016753:Interleukin-10; D018664:Interleukin-12; D015232:Dinoprostone