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Stress Enhances Airway Reactivity and Airway Inflammation in an Animal Model of Allergic Bronchial Asthma

From the Department of Internal Medicine, Charité-Campus Virchow, Humboldt University (R.A.J., P.C.A., B.F.K.), Berlin; Department of Pediatrics, Charité-Campus Virchow, Humboldt University (D.Q.), Berlin; and Department of Clinical Chemistry and Molecular Diagnostic, Philipps-Universität (U.H., H.R.), Marburg, Germany.

Address reprint requests to: Ricarda Joachim, MD, Charité-Campus Virchow, Biomedizinisches, Forschungszentrum, R. 2.0594, Augustenburger Platz 1, 13353 Berlin, Germany. Email: ricarda.joachim{at}charite.de

OBJECTIVE: Despite the long-standing clinical assumption that stress and asthma morbidity are associated, convincing experimental evidence on mechanisms has been unavailable. A wide range of immunological, endocrinological, and neuronal pathways are known to mediate and modulate a systemic stress response. Interestingly, most of these mediators play a crucial role in initiating and perpetuating symptoms associated with bronchial asthma. To explore potential mechanisms linking stress to asthma exacerbation we developed an animal model that combines allergic airway inflammation and exposure to stress.

METHODS: CBA/J mice were sensitized by intraperitoneal injection of ovalbumin (OVA) and challenged with OVA aerosol via the airways. Additionally, some mice were stressed by exposure to an ultrasonic stressor. Airway hyperreactivity (AHR) was measured in vitro by electric field stimulation (EFS) of tracheal smooth muscle elements. Bronchoalveolar lavage fluid (BAL) was obtained and cell numbers determined. Cytokine levels of IL-4, IL-5, and IFN- in BAL were determined by ELISA.

RESULTS: Our findings demonstrate that exogenously applied stress dramatically enhances airway reactivity in OVA-sensitized and challenged mice. Further, stress significantly increases allergen-induced airway inflammation identified by increased leukocyte (ie, eosinophil) numbers in bronchoalveolar lavage fluids.

CONCLUSIONS: We found further evidence that stress can indeed exacerbate airway hyperreactivity and airway inflammation in an animal model of allergic bronchial asthma and now introduce a novel murine model to identify stress-triggered pathways, including mediators as neurohormones, neuropeptides, and markers of inflammation.

Key Words: sonic stress, • allergic asthma, • airway inflammation, • airway hyperreactivity, • mouse model.

Abbreviations: AHR = airway hyperreactivity; AR = airway reactivity; BAL = bronchoalveolar lavage; EFS = electrical field stimulation; ELISA = enzyme linked immuno sorbent assay; ES₅₀ = frequency of half maximal tracheal contraction; GM-CSF = granulocyte-macrophage colony-stimulating factor; IFN = Interferon; IL = Interleukin; IP = intraperitoneal; LaGetSi = Landesamt für Arbeitsschutz, Gesundheitsschutz und technische Sicherheit Berlin (authority for animal research conduct); OVA = Ovalbumin; PBS = phosphate buffered saline; Th1/Th2 = T helper cell type 1 and 2; TNF = tumor necrosis factor; VCAM-1 = vascular cell adhesion molecule-1

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