Neonatal hyperoxia enhances the inflammatory response in adult mice infected with influenza A virus

Michael A. O'Reilly, Shauna H. Marr, Min Yee, Sharon A McGrath-Morrow, B. Paige Lawrence

Research output: Contribution to journalArticle

Abstract

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-γ, IL-1β, IL-6, tumor necrosis factor-α, KC, granulocyte-macrophage colony-stimulating factor, and macrophage inflammatory protein-1α, 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.

Original languageEnglish (US)
Pages (from-to)1103-1110
Number of pages8
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume177
Issue number10
DOIs
StatePublished - May 15 2008

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Hyperoxia
Influenza A virus
Bronchopulmonary Dysplasia
Virus Diseases
Respiratory Tract Infections
Lung
Air
Newborn Infant
Inflammation
Macrophage Inflammatory Proteins
Chemokine CCL2
Therapeutic Irrigation
Granulocyte-Macrophage Colony-Stimulating Factor
Infection
Interleukin-1
Survivors
Siblings
Interleukin-6
Neutrophils
Fibrosis

Keywords

  • Bronchopulmonary dysplasia
  • Hyperoxia
  • Infection
  • Lung inflammation
  • Virus

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

Neonatal hyperoxia enhances the inflammatory response in adult mice infected with influenza A virus. / O'Reilly, Michael A.; Marr, Shauna H.; Yee, Min; McGrath-Morrow, Sharon A; Lawrence, B. Paige.

In: American Journal of Respiratory and Critical Care Medicine, Vol. 177, No. 10, 15.05.2008, p. 1103-1110.

Research output: Contribution to journalArticle

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