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

Dietary aflatoxin B-1 (AFB(1)) exposure impairs innate and acquired ho st defenses resulting in increased susceptibility to infections in dom esticated animals. Experimental studies have confirmed this observatio n by demonstrating the immunosuppressive effects of AFB(1) ingestion. In addition to being present in dietary components, AFB(1) is also fou nd in significant amounts in respirable particles of grain dust. To de termine the effect of respiratory tract exposure to AFB(1) on host def enses, rats and mice were exposed either by aerosol inhalation or intr atracheal instillation to AFB(1). Nose-only inhalation exposure of rat s to AFB(1) aerosols suppressed alveolar macrophage (AM) phagocytosis at an estimated dose of 16.8 mu g/kg with the effect persisting for ap proximately 2 weeks. To determine whether another mode of respiratory tract exposure, intratracheal instillation, reflected inhalation expos ure, animals were treated with increasing concentrations of AFB(1) whi ch also suppressed AM phagocytosis in a dose-related manner albeit at doses at least an order of magnitude more than that obtained by aeroso l inhalation. Intratracheal administration of AFB(1) also suppressed t he release of tumor necrosis factor-alpha from AMs and impaired system ic innate and acquired immune defenses as shown, respectively, by supp ression of peritoneal macrophage phagocytosis and the primary splenic antibody response. These findings demonstrate that experimental respir atory tract exposure to AFB(1) suppresses pulmonary and systemic host defenses and indicates that inhalation exposure to AFB(1) is an occupa tional hazard where exposure to AFB(1)-laden dust is common. (C) 1994 Academic Press, Inc.