期刊
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
卷 177, 期 10, 页码 1103-1110出版社
AMER THORACIC SOC
DOI: 10.1164/rccm.200712-1839OC
关键词
bronchopulmonary dysplasia; hyperoxia; infection; lung inflammation; virus
资金
- NHLBI NIH HHS [R01-HL067392] Funding Source: Medline
- NIEHS NIH HHS [P30-ES01247, K02-ES012409, P30 ES001247, R21-ES013863] Funding Source: Medline
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 (BIRD) 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-1 beta, IL-6, tumor necrosis factor-alpha, KC, granulocyte-macrophage colony--stimulating factor, and macrophage inflammatory protein-1 alpha, 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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据