Neonatal Hyperoxia Enhances the Inflammatory Response in Adult Mice Infected with Influenza A Virus

• Published in: American journal of respiratory and critical care medicine 2008-05, Vol.177 (10), p.1103-1110
• Main Authors: O'Reilly, Michael A, Marr, Shauna H, Yee, Min, McGrath-Morrow, Sharon A, Lawrence, B. Paige
• Format: Article
• Language: English
• Subjects: Adult; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Animals; Animals, Newborn; Antibodies; Biological and medical sciences; Blood. Blood and plasma substitutes. Blood products. Blood cells. Blood typing. Plasmapheresis. Apheresis; Bronchopulmonary Dysplasia - complications; Bronchopulmonary Dysplasia - immunology; Bronchopulmonary Dysplasia - pathology; C. Pediatrics and Lung Development; Chemokines; Disease Models, Animal; Female; Humans; Hyperoxia; Hyperoxia - immunology; Hyperoxia - pathology; Infant, Newborn; Infections; Inflammation; Influenza; Influenza A virus; Influenza A virus - immunology; Intensive care medicine; Lavage; Leukocytes; Lung diseases; Lungs; Lymphatic system; Lymphocyte Count; Lymphocyte Subsets; Medical sciences; Mice; Mortality; Newborn babies; Orthomyxoviridae Infections - complications; Orthomyxoviridae Infections - immunology; Orthomyxoviridae Infections - pathology; Pathogens; Pneumonia - immunology; Pneumonia - pathology; Pneumonia - virology; Premature babies; Premature birth; Pulmonary Alveoli - pathology; Smooth muscle; Surfactants; Transfusions. Complications. Transfusion reactions. Cell and gene therapy; Viral infections; Viruses
• ISSN: 1073-449X; 1535-4970
• DOI: 10.1164/rccm.200712-1839OC

Lungs of adult mice exposed to hyperoxia as newborns are simplified and exhibit reduced function much like that observed in people who had bronchopulmonary dysplasia (BPD) as infants. Because survivors of BPD also show increased risk for symptomatic respiratory infections, we investigated how neonatal hyperoxia affected the response of adult mice infected with influenza A virus infection. To determine whether neonatal hyperoxia increased the severity of influenza A virus infection in adult mice. Adult female mice exposed to room air or hyperoxia between Postnatal Days 1 and 4 were infected with a sublethal dose of influenza A virus. The number of macrophages, neutrophils, and lymphocytes observed in airways of infected mice that had been exposed to hyperoxia as neonates was significantly greater than in infected siblings that had been exposed to room air. Enhanced inflammation correlated with increased levels of monocyte chemotactic protein-1 (CCL2) in lavage fluid, whereas infection-associated changes in IFN-gamma, IL-1beta, IL-6, tumor necrosis factor-alpha, KC, granulocyte-macrophage colony-stimulating factor, and macrophage inflammatory protein-1alpha, and production of virus-specific antibodies, were largely unaffected. Increased mortality of mice exposed to neonatal hyperoxia occurred by Day 14 of infection, and was associated with persistent inflammation and fibrosis. These data suggest that the disruptive effect of hyperoxia on neonatal lung development also reprograms key innate immunoregulatory pathways in the lung, which may contribute to exacerbated pathology and poorer resistance to respiratory viral infections typically seen in people who had BPD.