Stress enhances airway reactivity and airway inflammation in an animal model of allergic bronchial asthma.
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-gamma 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.
D000336:Aerosols; D000818:Animals; D001249:Asthma / Q000276:immunology / Q000503:physiopathology*; D016535:Bronchial Hyperreactivity / Q000209:etiology* / Q000503:physiopathology / Q000523:psychology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D004195:Disease Models, Animal; D004558:Electric Stimulation; D007114:Immunization; D007249:Inflammation; D051379:Mice; D008808:Mice, Inbred CBA; D009130:Muscle, Smooth / Q000503:physiopathology; D009622:Noise / Q000009:adverse effects; D010047:Ovalbumin / Q000008:administration & dosage / Q000633:toxicity; D011897:Random Allocation; D012137:Respiratory System / Q000276:immunology / Q000503:physiopathology*; D013315:Stress, Psychological / Q000276:immunology / Q000503:physiopathology*; D014132:Trachea / Q000503:physiopathology
D000336:Aerosols; D010047:Ovalbumin