Respiratory aflatoxicosis: suppression of pulmonary and systemic host defenses in rats and mice.
Dietary aflatoxin B1 (AFB1) exposure impairs innate and acquired host defenses resulting in increased susceptibility to infections in domesticated animals. Experimental studies have confirmed this observation by demonstrating the immunosuppressive effects of AFB1 ingestion. In addition to being present in dietary components, AFB1 is also found in significant amounts in respirable particles of grain dust. To determine the effect of respiratory tract exposure to AFB1 on host defenses, rats and mice were exposed either by aerosol inhalation or intratracheal instillation to AFB1. Nose-only inhalation exposure of rats to AFB1 aerosols suppressed alveolar macrophage (AM) phagocytosis at an estimated dose of 16.8 micrograms/kg with the effect persisting for approximately 2 weeks. To determine whether another mode of respiratory tract exposure, intratracheal instillation, reflected inhalation exposure, animals were treated with increasing concentrations of AFB1 which also suppressed AM phagocytosis in a dose-related manner albeit at doses at least an order of magnitude more than that obtained by aerosol inhalation. Intratracheal administration of AFB1 also suppressed the release of tumor necrosis factor-alpha from AMs and impaired systemic innate and acquired immune defenses as shown, respectively, by suppression of peritoneal macrophage phagocytosis and the primary splenic antibody response. These findings demonstrate that experimental respiratory tract exposure to AFB1 suppresses pulmonary and systemic host defenses and indicates that inhalation exposure to AFB1 is an occupational hazard where exposure to AFB1-laden dust is common.
Jakab
G J
GJ
Department of Environmental Health Sciences, Johns Hopkins School of Hygiene and Public Health, Baltimore, Maryland 21205-2179.
Hmieleski
R R
RR
Zarba
A
A
Hemenway
D R
DR
Groopman
J D
JD
D000280:Administration, Inhalation; D016604:Aflatoxin B1 / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D000917:Antibody Formation; D005260:Female; D007442:Intubation, Intratracheal; D008168:Lung / Q000187:drug effects / Q000473:pathology; D016676:Macrophages, Alveolar / Q000187:drug effects; D017737:Macrophages, Peritoneal / Q000187:drug effects; D008297:Male; D051379:Mice; D015651:Mycotoxicosis / Q000209:etiology* / Q000276:immunology; D010587:Phagocytosis / Q000187:drug effects; D051381:Rats; D011916:Rats, Inbred F344; D011961:Receptors, Fc; D012137:Respiratory System / Q000187:drug effects* / Q000276:immunology; D013154:Spleen / Q000187:drug effects / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D011961:Receptors, Fc; D014409:Tumor Necrosis Factor-alpha; D016604:Aflatoxin B1