Document Detail


Neonatal hyperoxia enhances the inflammatory response in adult mice infected with influenza A virus.
MedLine Citation:
PMID:  18292469     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Michael A O'Reilly; Shauna H Marr; Min Yee; Sharon A McGrath-Morrow; B Paige Lawrence
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2008-02-21
Journal Detail:
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:
Created Date:  2008-05-07     Completed Date:  2008-05-21     Revised Date:  2013-06-25    
Medline Journal Info:
Nlm Unique ID:  9421642     Medline TA:  Am J Respir Crit Care Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1103-10     Citation Subset:  AIM; IM    
Affiliation:
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:
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:
K02-ES012409/ES/NIEHS NIH HHS; P30 ES001247/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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