Systemic immunotoxicity in AJ mice following 6-month whole body inhalation exposure to diesel exhaust.
The purpose of these studies was to determine the effects of subchronic diesel exposure on indicators of systemic immunity in mice. AJ mice were exposed daily for 6 months (6 h/day) to atmospheres containing one of four concentrations (30, 100, 300, and 1000 microg/m(3)) of diluted diesel exhaust (DE) in whole body exposure chambers. The effects of DE were compared to chamber exposure controls receiving fresh air. DE was assessed for effects on systemic immunity by measuring the proliferative response of spleen cells following stimulation with T cell (phytohemagglutinin, or PHA) or B cell (lipopolysaccharide, or LPS) mitogens. The results showed that DE at all exposure levels suppressed the proliferative response of T cells. B cell proliferation was increased at 30 microg/m(3) and was unaffected at the 100, 300, and 1000 microg/m(3) exposures. Polycyclic aromatic hydrocarbons (PAHs) are known to suppress spleen cell mitogenic responses, and it has been hypothesized by several groups that PAHs and perhaps benzo(a)pyrene (BaP)-quinones (BPQs) may be responsible for the effects of DE or diesel exhaust particles (DEP). Therefore, a second purpose of these studies was to determine the effects of in vitro BPQs on AJ mouse spleen cell mitogenic responses and compare to DE in preliminary studies. Unlike DE, BPQs were found to increase T cell proliferation. In addition, analysis of chamber atmospheres showed that there was little if any PAH and BPQs in DE. Therefore, these results demonstrate that because of the absence of BPQs in DE, they are likely not responsible for the immunosuppressive effect of DE on murine spleen cell responses.
Burchiel
Scott W
SW
College of Pharmacy Toxicology Program, University of New Mexico, MSC09-5360, Room 64B, 2502 Marble NE, Albuquerque, NM 87131, USA. sburchiel@salud.nm.edu
Lauer
Fredine T
FT
McDonald
Jacob D
JD
Reed
Matthew D
MD
D000280:Administration, Inhalation; D000818:Animals; D001273:Atmosphere Exposure Chambers; D004305:Dose-Response Relationship, Drug; D051379:Mice; D011084:Polycyclic Aromatic Hydrocarbons / Q000032:analysis; D013154:Spleen / Q000187:drug effects* / Q000276:immunology; D001335:Vehicle Emissions / Q000032:analysis / Q000633:toxicity*
D011084:Polycyclic Aromatic Hydrocarbons; D001335:Vehicle Emissions