Substance P as prophylaxis for JP-8 jet fuel-induced immunotoxicity.
Previous studies have shown that short-term, low-concentration JP-8 exposure had significant effects on the immune system that persisted for extended periods of time. It was found that administration of aerosolized substance P (SP) was able to protect exposed animals from JP-8-induced immune changes, whereas administration of SP antagonists compounded the deleterious effects ofjet fuel exposure. Thus, SP administration appears to be a relatively simple and efficient means to reverse the immunotoxicity due to hydrocarbon exposure. In the current study, aerosolized SP was analyzed for its potential prophylactic ability to counteract JP-8-induced immunotoxicity. It was observed that concentrations as low as 1 nM were effective in ameliorating the effects of JP-8 exposure on the immune system. SP administered before JP-8 exposure could prophylactically protect both the spleen and thymus from significant organ weight loss, but could not completely restore immune cell numbers to normal, baseline levels. Furthermore, SP treatment could be delayed as long as 1 h postexposure and reverse the effects of jet fuel exposure on immune organ weight loss and immune cell recovery. Significantly, SP could be given 15 min pre-JP-8 exposure but neither 1 nor 6 h pre-JP-8 exposure, and prevent immune dysfunction as measured in mitogenesis assays. However, SP could be delayed up to 6 h post-JP-8 exposure and still almost completely restore immune function. Thus, SP appears able to both prevent and reverse the immunotoxicological effects associated with JP-8 exposure. These results also provide insight into the manner in which JP-8 jet fuel mediates its effects on the immune system.
Harris
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DT
Department of Microbiology and Immunology University of Arizona, Tucson 85721, USA. davidh@u.arizona.edu
Sakiestewa
D
D
Titone
D
D
Robledo
R F
RF
Young
R S
RS
Witten
M
M
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D006838:Hydrocarbons / Q000008:administration & dosage / Q000633:toxicity*; D007154:Immune System Diseases / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control*; D000922:Immunotoxins / Q000008:administration & dosage / Q000633:toxicity*; D019570:Inhalation Exposure / Q000009:adverse effects; D051379:Mice; D008810:Mice, Inbred C57BL; D009929:Organ Size / Q000187:drug effects; D020127:Recovery of Function / Q000187:drug effects; D013154:Spleen / Q000473:pathology; D013373:Substance P / Q000494:pharmacology*; D013950:Thymus Gland / Q000473:pathology
D006838:Hydrocarbons; D000922:Immunotoxins; C098607:JP8 aviation fuel; D013373:Substance P