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Endotoxin inhalation alters lung development in neonatal mice

Authors

  • Katarina Kulhankova MD, PhD, MS,

    1. Department of Occupational and Environmental Health, University of Iowa, Iowa City, Iowa
    2. Environmental Health Sciences Research Center, University of Iowa, Iowa City, Iowa
    3. Department of Pathology, University of Iowa, Iowa City, Iowa
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  • Caroline L.S. George MD,

    1. Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota
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  • Joel N. Kline MD, Msc,

    1. Department of Occupational and Environmental Health, University of Iowa, Iowa City, Iowa
    2. Environmental Health Sciences Research Center, University of Iowa, Iowa City, Iowa
    3. Department of Internal Medicine, University of Iowa, Iowa City, Iowa
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  • Melissa Darling BS,

    1. Iowa Biotechnology Association, Des Moines, Iowa
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  • Peter S. Thorne MS, PhD

    Corresponding author
    1. Department of Occupational and Environmental Health, University of Iowa, Iowa City, Iowa
    2. Environmental Health Sciences Research Center, University of Iowa, Iowa City, Iowa
    • Department of Occupational and Environmental Health, College of Public Health, The University of Iowa, S341A CPHB, Iowa City, IA 52242.
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  • Disclosure Statement: The authors report no conflicts of interests.

Abstract

Background

Childhood asthma is a significant public health problem. Epidemiologic evidence suggests an association between childhood asthma exacerbations and early life exposure to environmental endotoxin. Although the pathogenesis of endotoxin-induced adult asthma is well studied, questions remain about the impact of environmental endotoxin on pulmonary responsiveness in early life.

Methods

We developed a murine model of neonatal/juvenile endotoxin exposures approximating those in young children and evaluated the lungs inflammatory and remodeling responses.

Results

Persistent lung inflammation induced by the inhalation of endotoxin in early life was demonstrated by the influx of inflammatory cells and pro-inflammatory mediators to the airways and resulted in abnormal alveolarization.

Conclusions

Results of this study advance the understanding of the impact early life endotoxin inhalation has on the lower airways, and demonstrates the importance of an experimental design that approximates environmental exposures as they occur in young children. Am. J. Ind. Med. 55:1146–1158, 2012. © 2012 Wiley Periodicals, Inc.

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