ToxSci Advance Access originally published online on September 26, 2003
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Toxicological Sciences 76, 347-356 (2003)
Copyright © 2003 by the Society of Toxicology
IMMUNOTOXICOLOGY |
Immunological Function in Mice Exposed to JP-8 Jet Fuel In Utero
,1
,,¶
* National Institute for Occupational Safety and Health, Morgantown, West Virginia 26505;
Environmental Health Science, University of South Carolina-Beaufort, Beaufort, South Carolina 29902;
Department of Health Professions,
Marine Biomedicine and Environmental Science Center, and
¶ Department of Medicine/Pediatrics, Medical University of South Carolina, Charleston, South Carolina 29425.
Immunological parameters, host resistance, and thyroid hormones were evaluated in F1 mice exposed in utero to jet propulsion fuel–8 (JP-8). C57BL/6 pregnant dams (mated with C3H/HeJ males) were gavaged daily on gestation days 6–15 with JP-8 in a vehicle of olive oil at 0, 1000, or 2000 mg/kg. At weaning (3 weeks of age), no significant differences were observed in body, liver, spleen, or thymus weight, splenic and thymic cellularity, splenic CD4/CD8 lymphocyte subpopulations, or T-cell proliferation. Yet, lymphocytic proliferative responses to B-cell mitogens were suppressed in the 2000 mg/kg treatment group. In addition, thymic CD4-/CD8+ cells were significantly increased. By adulthood (8 weeks of age), lymphocyte proliferative responses and the alteration in thymic CD4-/CD8+ cells had returned to normal. However, splenic weight and thymic cellularity were altered, and the IgM plaque forming cell response was suppressed by 46% and 81% in the 1000 and 2000 mg/kg treatment groups, respectively. Furthermore, a 38% decrease was detected in the total T4 serum hormone level at 2000 mg/kg. In F1 adults, no significant alterations were observed in natural killer cell activity, T-cell lymphocyte proliferation, bone marrow cellularity and proliferative responses, complete blood counts, peritoneal and splenic cellularity, liver, kidney, or thymus weight, macrophage phagocytosis or nitric oxide production, splenic CD4/CD8 lymphocyte subpopulations, or total T3 serum hormone levels. Host resistance models in treated F1 adults demonstrated that immunological responses were normal after challenge with Listeria monocytogenes, but heightened susceptibility to B16F10 tumor challenge was seen at both treatment levels. This study demonstrates that prenatal exposure to JP-8 can target the developing murine fetus and result in impaired immune function and altered T4 levels in adulthood.
Key Words: immunological parameters; host resistance; jet propulsion fuel-8; JP-8, thyroid hormones.
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