Neonatal hyperoxia increases airway reactivity and inflammation in adult mice

Summary Background Supplemental O2 to treat bronchopulmonary dysplasia (BPD) in premature infants, is a major risk factor producing alteration in lung function, airway reactivity, and predisposition to respiratory infections. This study explores inflammatory and airway responses following neonatal h...

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Published in:Pediatric pulmonology 2016-11, Vol.51 (11), p.1131-1141
Main Authors: Kumar, Vasantha H.S., Lakshminrusimha, Satyan, Kishkurno, Sergei, Paturi, Babu S., Gugino, Sylvia F., Nielsen, Lori, Wang, Huamei, Ryan, Rita M.
Format: Article
Language:English
Subjects:
airway reactivity
Animals
Animals, Newborn
Biomarkers - metabolism
Chemokine CCL2 - metabolism
cytokines
hyperoxia
Hyperoxia - complications
Hyperoxia - metabolism
Hyperoxia - physiopathology
inflammation
Interleukin-12 - metabolism
Lung - metabolism
Lung - physiopathology
lymphocytes
Lymphocytes - metabolism
Methacholine Chloride
Mice
Muscle, Smooth - metabolism
Muscle, Smooth - physiopathology
Oxygen
Pneumonia - etiology
Pneumonia - metabolism
Pneumonia - physiopathology
Vascular Endothelial Growth Factor A - metabolism
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Summary:Summary Background Supplemental O2 to treat bronchopulmonary dysplasia (BPD) in premature infants, is a major risk factor producing alteration in lung function, airway reactivity, and predisposition to respiratory infections. This study explores inflammatory and airway responses following neonatal hyperoxia in adult mice. Methods Newborn mouse litters were randomized to 85% O2 or room air (RA) on P3 for 12 days; mice were sacrificed either on P15 or at 15 weeks following recovery in RA. Airway hyper reactivity (AHR) was assessed in vivo (8 and 12 weeks) and in vitro (15 weeks) with methacholine; Lung and BAL were assayed for inflammatory mediators, cell counts, CD3 immunohistochemistry, and histopathology. Results Hyperoxic mice had increased airway reactivity at baseline and following methacholine challenge in vivo (8 and 12 weeks); isolated tracheal rings had a significantly higher constriction response to methacholine in vitro compared to RA group. Inflammatory markers were higher at 2 weeks (MCP‐1, IL‐12, INF‐γ) and at 15 weeks (LTB4, VEGF); Lipoxin‐A4 was lower in the hyperoxia group at both time points. Increased airway smooth muscle thickness and angiogenesis in the lung was seen at 15 weeks. Hyperoxic lungs exhibited alveolar simplification at 2 and 15 weeks. Absolute lymphocyte count was higher in lavage fluid with an increased CD3 cell count at 15 weeks suggesting persistent inflammation in adult mice following neonatal hyperoxia. Conclusions Exposure to hyperoxia in newborn mice increases long‐term airway reactivity with persistent lung inflammation associated with a marked increase in lymphocytes, suggesting long‐term consequences in adults. Pediatr Pulmonol. 2016;51:1131–1141. © 2016 Wiley Periodicals, Inc.
ISSN:8755-6863
1099-0496
DOI:10.1002/ppul.23430