ABSTRACT
Animal infectivity models have been important in the demonstration of enhanced susceptibility to viral and bacterial infection as a result of low-level toxicant exposure. This study demonstrated an enhanced and prolonged viral infection using an influenza virus infectivity model in the rat following exposure to the toxicant gas phosgene. Fischer-344 rats exposed to either air or a sublethal concentration of phosgene demonstrated peak pulmonary influenza virus titers 1 d after infection. Virus titers in rats exposed to air declined rapidly falling below detectable levels by 4 d after infection. However, a significantly enhanced and prolonged pulmonary influenza virus infection was observed on d 3 and 4 after infection in rats exposed to phosgene. Virus was cleared below detectable limits on d 5 after infection in animals exposed to phosgene. Thus, inhalation of sublethal concentrations of phosgene resulted in an increased severity of pulmonary influenza virus infection. This study provides a demonstration of the effective use of a rat viral infectivity model to detect the immunotoxicity of inhaled pollutants. This model will allow future studies to focus on the immunological mechanism(s) responsible for the enhanced and prolonged pulmonary influenza virus infection.
Subject(s)
Immune Tolerance/drug effects , Influenza A virus/drug effects , Orthomyxoviridae Infections/immunology , Phosgene/toxicity , Administration, Inhalation , Animals , Bronchoalveolar Lavage Fluid/chemistry , Bronchoalveolar Lavage Fluid/cytology , Cell Count , Cell Survival/drug effects , Disease Models, Animal , Disease Susceptibility , Influenza A virus/physiology , Lung/drug effects , Lung/immunology , Lung/microbiology , Lymphocytes/drug effects , Macrophages/drug effects , Male , Neutrophils/drug effects , Phosgene/administration & dosage , Rats , Rats, Inbred F344 , Viral Plaque Assay , Virus Replication/drug effectsABSTRACT
Adult female B6C3F1 mice were given a single ip dose of 0, 01, 1.0, or 10.0 micrograms/kg 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and examined for immune function and host resistance 7-10 d later. Exposure to TCDD resulted in a significant dose-related decrease in induction of both IgM and IgG antibody-forming cells. This suppression was noted for both T-dependent and T-independent antigens. TCDD at a dosage of 10 micrograms/kg was shown to suppress production of antibody to viral hemagglutinin. In contrast, TCDD exposure had no significant effect on natural killer cell function, production of interferon, or various parameters of macrophage function. Assessment of host resistance revealed a significant increase in susceptibility to fatal infection with influenza virus, but no significant alteration in susceptibility to infection with the bacterium Listeria monocytogenes.
