title: Influenza virus infection, ozone exposure, and fibrogenesis.
abstract: Oxidant exposure following chemically induced lung injury exacerbates the tendency to develop pulmonary fibrosis. Influenza virus pneumonitis causes severe acute lung damage that, upon resolution, is followed by a persistent alveolitis and parenchymal changes characterized by patchy interstitial pneumonia and collagen deposition in the affected areas. To determine whether oxidant exposure exacerbates the virus-induced alveolitis and residual lung damage, mice were infected by aerosol inhalation with influenza A virus and continuously exposed to 0.5 ppm ozone or ambient air. Noninfected control mice were exposed to either ambient air or ozone. On various days during the first month after infection, groups of mice were sacrificed and their lungs assessed for acute injury (lung lavage albumin, total and differential cell counts, wet/dry ratios, and morphometry). At 30, 60, 90, and 120 days after infection, groups of mice were sacrificed for total and differential lavage cell counts, lung hydroxyproline content, and morphometric analysis. Ozone exposure did not alter the proliferation of virus in the lungs as quantitated by infectious virus titers of lung homogenates at 1, 4, 7, 10, and 15 days after virus infection but mitigated the virus-induced acute lung injury by approximately 50%. After Day 30 a shift in the character of the pulmonary lesions was observed in that continuous exposure to ozone potentiated the postinfluenzal alveolitis and structural changes in the lung parenchyma. Additional studies suggest that the mechanism for the enhanced postinfluenzal lung damage may be related to the oxidant impairing the repair process of the acute influenzal lung damage. These data demonstrate that ozone exposure mitigates acute virus-induced lung injury and potentiates residual lung damage.
authors.affiliation: Department of Environmental Health Sciences, Johns Hopkins School of Hygiene and Public Health, Baltimore, Maryland 21205.
authors.forename: G J
authors.initials: GJ
authors.lastname: Jakab
authors.forename: D J
authors.initials: DJ
authors.lastname: Bassett
mesh_terms: D000393:Air Pollutants; D000418:Albumins / Q000032:analysis; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000032:analysis; D005260:Female; D006909:Hydroxyproline / Q000032:analysis; D008168:Lung / Q000187:drug effects / Q000473:pathology*; D051379:Mice; D009976:Orthomyxoviridae Infections; D010126:Ozone / Q000633:toxicity*; D011024:Pneumonia, Viral / Q000473:pathology*; D011658:Pulmonary Fibrosis / Q000209:etiology / Q000473:pathology*
chemical_list: D000393:Air Pollutants; D000418:Albumins; D010126:Ozone; D006909:Hydroxyproline