| Neonatal hyperoxia enhances the inflammatory response in adult mice infected with influenza A virus. | |
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MedLine Citation:
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PMID: 18292469 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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RATIONALE: 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. OBJECTIVES: To determine whether neonatal hyperoxia increased the severity of influenza A virus infection in adult mice. METHODS: 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. MEASUREMENTS AND MAIN RESULTS: 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. CONCLUSIONS: 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. |
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Authors:
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Michael A O'Reilly; Shauna H Marr; Min Yee; Sharon A McGrath-Morrow; B Paige Lawrence |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2008-02-21 |
Journal Detail:
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Title: American journal of respiratory and critical care medicine Volume: 177 ISSN: 1535-4970 ISO Abbreviation: Am. J. Respir. Crit. Care Med. Publication Date: 2008 May |
Date Detail:
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Created Date: 2008-05-07 Completed Date: 2008-05-21 Revised Date: 2009-11-18 |
Medline Journal Info:
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Nlm Unique ID: 9421642 Medline TA: Am J Respir Crit Care Med Country: United States |
Other Details:
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Languages: eng Pagination: 1103-10 Citation Subset: AIM; IM |
Affiliation:
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Department of Pediatrics, Box 850, University of Rochester School of Medicine and Dentistry, 601 Elmwood Avenue, Rochester, NY 14642, USA. michael_oreilly@urmc.rochester.edu |
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| MeSH Terms | |
Descriptor/Qualifier:
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Adult Animals Animals, Newborn Bronchopulmonary Dysplasia / complications, immunology*, pathology Disease Models, Animal Female Humans Hyperoxia / immunology*, pathology Infant, Newborn Influenza A virus / immunology* Lymphocyte Count Lymphocyte Subsets Mice Orthomyxoviridae Infections / complications, immunology*, pathology Pneumonia* / immunology, pathology, virology Pulmonary Alveoli / pathology |
| Grant Support | |
ID/Acronym/Agency:
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K02-ES012409/ES/NIEHS NIH HHS; P30-ES01247/ES/NIEHS NIH HHS; R01-HL067392/HL/NHLBI NIH HHS; R21-ES013863/ES/NIEHS NIH HHS |
| Comments/Corrections | |
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