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

<jats:title>Summary</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Epidemiologic studies have reported an association between diesel exhaust particle (<jats:styled-content style="fixed-case">DEP</jats:styled-content>) exposure, allergic sensitization, and childhood wheezing, although the mechanisms remain unclear. While <jats:styled-content style="fixed-case">DEP</jats:styled-content> is known to augment allergic responses in adult animal models, its effects on sensitization and asthma severity in young animals is unknown.</jats:p></jats:sec><jats:sec><jats:title>Objective</jats:title><jats:p>To examine the impact of different doses of <jats:styled-content style="fixed-case">DEP</jats:styled-content> and allergen co‐exposure on allergic sensitization and asthma characteristics in young mice, and whether <jats:styled-content style="fixed-case">T</jats:styled-content>h17 as well as <jats:styled-content style="fixed-case">T</jats:styled-content>h2 responses are induced.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Lungs of 3‐week‐old wild‐type <jats:styled-content style="fixed-case">B</jats:styled-content>alb/c mice were exposed by pharyngeal aspiration nine times over 3 weeks to <jats:styled-content style="fixed-case">DEP</jats:styled-content> at 1.2 or 6.0 mg/kg body weight, house dust mite (<jats:styled-content style="fixed-case">HDM</jats:styled-content>) at 0.8, 1.2 or 6.0 mg/kg of <jats:styled-content style="fixed-case">DEP</jats:styled-content> in combination with <jats:styled-content style="fixed-case">HDM</jats:styled-content>, or the same volume (50 μL) of 0.9% sterile saline.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>In young mice, exposure to 1.2 mg/kg of <jats:styled-content style="fixed-case">DEP</jats:styled-content> caused no detectable lung inflammation, but 6.0 mg/kg of <jats:styled-content style="fixed-case">DEP</jats:styled-content> induced neutrophilic influx. Compared to <jats:styled-content style="fixed-case">HDM</jats:styled-content> or <jats:styled-content style="fixed-case">DEP</jats:styled-content> alone, mice exposed to either dose of <jats:styled-content style="fixed-case">DEP</jats:styled-content> together with <jats:styled-content style="fixed-case">HDM</jats:styled-content> demonstrated increased allergen‐specific <jats:styled-content style="fixed-case">I</jats:styled-content>g<jats:styled-content style="fixed-case">E</jats:styled-content>, lung inflammation, airway hyperreactivity, goblet cell metaplasia, <jats:styled-content style="fixed-case">T</jats:styled-content>h2/<jats:styled-content style="fixed-case">T</jats:styled-content>h17 cytokines, dendritic cells, activated <jats:styled-content style="fixed-case">T</jats:styled-content> cells, effector <jats:styled-content style="fixed-case">T</jats:styled-content> cells, and <jats:styled-content style="fixed-case">IL</jats:styled-content>‐17<jats:sup>pos</jats:sup> and <jats:styled-content style="fixed-case">IL</jats:styled-content>‐13<jats:sup>pos</jats:sup>/<jats:styled-content style="fixed-case">IL</jats:styled-content>‐17<jats:styled-content style="fixed-case">A</jats:styled-content><jats:sup>pos</jats:sup> <jats:styled-content style="fixed-case">T</jats:styled-content> effector cells.</jats:p></jats:sec><jats:sec><jats:title>Conclusions and Clinical Relevance</jats:title><jats:p>In young mice, co‐exposure to <jats:styled-content style="fixed-case">DEP</jats:styled-content> and <jats:styled-content style="fixed-case">HDM</jats:styled-content> together exacerbated allergic sensitization and induced key characteristics of more severe asthma, including <jats:styled-content style="fixed-case">IL</jats:styled-content>‐17<jats:styled-content style="fixed-case">A</jats:styled-content>,<jats:styled-content style="fixed-case"> IL</jats:styled-content>‐17<jats:sup>pos</jats:sup> and <jats:styled-content style="fixed-case">IL</jats:styled-content>‐13<jats:sup>pos</jats:sup>/<jats:styled-content style="fixed-case">IL</jats:styled-content>‐17<jats:styled-content style="fixed-case">A</jats:styled-content><jats:sup>pos</jats:sup> <jats:styled-content style="fixed-case">T</jats:styled-content> effector cells. While exposure to 1.2 mg/kg <jats:styled-content style="fixed-case">DEP</jats:styled-content> alone caused no detectable changes, it did exacerbate allergic sensitization and asthma characteristics to a similar degree as a five‐fold higher dose of <jats:styled-content style="fixed-case">DEP</jats:styled-content>. This study demonstrates that exposure to <jats:styled-content style="fixed-case">DEP</jats:styled-content>, 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.</jats:p></jats:sec>