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Clinical & Experimental Allergy

Diesel exhaust particle exposure increases severity of allergic asthma in young mice

Authors

  • T. H. Acciani,

    1. Division of Pulmonary Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
    2. Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA
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  • E. B. Brandt,

    1. Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA
    2. Division of Asthma Research, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
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  • G. K. Khurana Hershey,

    1. Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA
    2. Division of Asthma Research, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
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  • T. D. Le Cras

    Corresponding author
    1. Division of Pulmonary Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
    2. Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA
    • Correspondence:

      Timothy D. Le Cras, Division of Pulmonary Biology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave, Cincinnati, OH 45229, USA.

      E-mail: tim.lecras@cchmc.org

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Summary

Background

Epidemiologic studies have reported an association between diesel exhaust particle (DEP) exposure, allergic sensitization, and childhood wheezing, although the mechanisms remain unclear. While DEP is known to augment allergic responses in adult animal models, its effects on sensitization and asthma severity in young animals is unknown.

Objective

To examine the impact of different doses of DEP and allergen co-exposure on allergic sensitization and asthma characteristics in young mice, and whether Th17 as well as Th2 responses are induced.

Methods

Lungs of 3-week-old wild-type Balb/c mice were exposed by pharyngeal aspiration nine times over 3 weeks to DEP at 1.2 or 6.0 mg/kg body weight, house dust mite (HDM) at 0.8, 1.2 or 6.0 mg/kg of DEP in combination with HDM, or the same volume (50 μL) of 0.9% sterile saline.

Results

In young mice, exposure to 1.2 mg/kg of DEP caused no detectable lung inflammation, but 6.0 mg/kg of DEP induced neutrophilic influx. Compared to HDM or DEP alone, mice exposed to either dose of DEP together with HDM demonstrated increased allergen-specific IgE, lung inflammation, airway hyperreactivity, goblet cell metaplasia, Th2/Th17 cytokines, dendritic cells, activated T cells, effector T cells, and IL-17pos and IL-13pos/IL-17Apos T effector cells.

Conclusions and Clinical Relevance

In young mice, co-exposure to DEP and HDM together exacerbated allergic sensitization and induced key characteristics of more severe asthma, including IL-17A, IL-17pos and IL-13pos/IL-17Apos T effector cells. While exposure to 1.2 mg/kg DEP alone caused no detectable changes, it did exacerbate allergic sensitization and asthma characteristics to a similar degree as a five-fold higher dose of DEP. This study demonstrates that exposure to DEP, even at a dose that alone causes no inflammation, exacerbates allergic asthma in young animals and suggests the importance of preventive measures to reduce the exposure of children to traffic related air pollution.

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