RESPIRATORY AFLATOXICOSIS - SUPPRESSION OF PULMONARY AND SYSTEMIC HOST DEFENSES IN RATS AND MICE

Dietary aflatoxin B-1 (AFB(1)) 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 AFB(1) ingestion. In addition to being present in dietary components, AFB(1) is also found in significant amounts in respirable particles of grain dust. To determine the effect of respiratory tract exposure to AFB(1) on host defenses, rats and mice were exposed either by aerosol inhalation or intratracheal instillation to AFB(1). Nose-only inhalation exposure of rats to AFB(1) aerosols suppressed alveolar macrophage (AM) phagocytosis at an estimated dose of 16.8 mu g/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 AFB(1) 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 AFB(1) 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 AFB(1) suppresses pulmonary and systemic host defenses and indicates that inhalation exposure to AFB(1) is an occupational hazard where exposure to AFB(1)-laden dust is common. (C) 1994 Academic Press, Inc.