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Title: Lung development and the host response to influenza A virus are altered by different doses of neonatal oxygen in mice.

Authors: Buczynski, Bradley W; Yee, Min; Paige Lawrence, B; O'Reilly, Michael A

Published In Am J Physiol Lung Cell Mol Physiol, (2012 May 15)

Abstract: Oxygen exposure in preterm infants has been associated with altered lung development and increased risk for respiratory viral infections later in life. Although the dose of oxygen sufficient to exert these changes in humans remains unknown, adult mice exposed to 100% oxygen between postnatal days 1-4 exhibit alveolar simplification and increased sensitivity to influenza virus infection. Additionally, two nonlinear thresholds of neonatal oxygen exposures were previously identified that promote modest (between 40% and 60% oxygen) and severe (between 80% and 100% oxygen) changes in lung development. Here, we investigate whether these two thresholds correlate with the severity of lung disease following respiratory viral infection. Adult mice exposed to 100% oxygen at birth, and to a lesser extent 80% oxygen, demonstrated enhanced body weight loss, persistent inflammation, and fibrosis following infection compared with infected siblings exposed to room air at birth. In contrast, the host response to infection was indistinguishable between mice exposed to room air and 40% or 60% oxygen. Interestingly, levels of monocyte chemoattractant protein (MCP)-1 were equivalently elevated in infected mice that had been exposed to 80% or 100% oxygen as neonates. However, reducing levels of MCP-1 using heterozygous Mcp-1 mice did not affect oxygen-dependent changes in the response to infection. Thus lung development and the host response to respiratory viral infection are disrupted by different doses of oxygen. Our findings suggest that measuring lung function alone may not be sufficient to identify individuals born prematurely who have increased risk for respiratory viral infection.

PubMed ID: 22408042 Exiting the NIEHS site

MeSH Terms: Animals; Animals, Newborn; Chemokine CCL2/biosynthesis; Female; Hyperoxia/complications*; Hyperoxia/immunology; Hyperoxia/virology; Inflammation/complications; Inflammation/immunology; Inflammation/virology; Influenza A virus/physiology; Lung/growth & development; Lung/immunology*; Lung/virology; Mice; Orthomyxoviridae Infections/complications; Orthomyxoviridae Infections/immunology; Orthomyxoviridae Infections/virology; Oxidative Stress; Oxygen/adverse effects*; Oxygen/metabolism; Pulmonary Fibrosis/complications; Pulmonary Fibrosis/immunology; Pulmonary Fibrosis/virology; Severity of Illness Index; Weight Loss

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