Opposing effects of short- and long-term stress on airway inflammation.
Between 20% and 35% of subjects with asthma experience asthma exacerbations during periods of stress. The biological mechanisms underlying these exacerbations are not clearly understood, and the role of psychologic factors in the pathophysiology of asthma remains controversial. We investigated the ability of psychologic stress to modulate airway inflammation and airway hyperresponsiveness (AHR) to methacholine in a murine model of asthma. Animals were exposed to a stressor daily for 3 (short-term stress) or 7 (long-term stress) days. After allergen challenge, AHR was assessed through plethysmography, and bronchoalveolar lavage cells were counted as a measure of inflammation. After short-term stress, inflammatory cell number was decreased compared with unstressed animals, whereas levels of interleukin (IL)-6, IL-9, and IL-13 were increased. Administration of a corticosteroid receptor antagonist, before stress, prevented the decrease in inflammatory cell numbers. In contrast, animals stressed for 7 consecutive days showed a significant increase in inflammatory cell numbers, which was independent of the glucocorticoid response, but no change in cytokine levels. AHR was not altered in stressed animals. Our results indicate that repeated exposure to stress over the long term engages different mechanisms than short-term stress and can exacerbate the chronic inflammatory responses of the airway.
Forsythe
Paul
P
Pulmonary Research Group, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada.
Ebeling
Cory
C
Gordon
John R
JR
Befus
A Dean
AD
Vliagoftis
Harissios
H
D000485:Allergens / Q000276:immunology; D000818:Animals; D001249:Asthma / Q000473:pathology / Q000503:physiopathology* / Q000523:psychology; D016535:Bronchial Hyperreactivity / Q000503:physiopathology; D001985:Bronchial Provocation Tests; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D016207:Cytokines / Q000032:analysis; D007249:Inflammation; D008297:Male; D016210:Methacholine Chloride; D051379:Mice; D008807:Mice, Inbred BALB C; D015735:Mifepristone / Q000494:pharmacology; D011987:Receptors, Steroid / Q000037:antagonists & inhibitors; D013312:Stress, Physiological / Q000503:physiopathology*
D000485:Allergens; D016207:Cytokines; D011987:Receptors, Steroid; D016210:Methacholine Chloride; D015735:Mifepristone