The involvement of glucocorticoids in psychological stress-induced exacerbations of experimental allergic asthma.
BACKGROUND
Psychological stress is associated with the aggravation of asthma symptoms. Glucocorticoids (GC), which are stress hormones released upon exposure to stress, have the potential to shift immune responses towards a predominant Th2 response by priming antigen-presenting cells to produce lower levels of IL-12 as well as reducing the development of regulatory T cells. However, the involvement of GC in psychological stress-induced exacerbations of allergic asthma has not yet been clarified.


METHODS
Sensitized mice were exposed to restraint stress followed by forced swimming stress, during which a GC receptor antagonist or a GC synthesis inhibitor was administered, and then antigen was inhaled. Corticosterone levels in the blood were measured in stressed and nonstressed mice. After antigen inhalation, the airway responses to aerosolized methacholine, epithelial mucus secretion and airway inflammation were evaluated, and the IL-13 contents in bronchoalveolar lavage fluid were measured.


RESULTS
The exposure to stress significantly increased corticosterone levels. Allergic airway responses and the increase of IL-13 contents evoked by antigen inhalation were significantly higher in stressed mice than in nonstressed mice. The administration of a GC receptor antagonist and a GC synthesis inhibitor during stress exposure significantly reduced the exacerbation of the airway responses and the increase of IL-13 contents in stressed mice challenged with antigen.


CONCLUSIONS
These results indicate that the increased release of GC upon exposure to stress has a priming effect on the aggravation of allergic airway responses following the exposure, suggesting a pathophysiological role for the neuroendocrine axis in linking psychological stress to asthma exacerbations.
Department of Pathophysiology, Tohoku Pharmaceutical University, Sendai, Japan.
Kaori
K
Okuyama
Kazuhisa
K
Dobashi
Tomomitsu
T
Miyasaka
Naoki
N
Yamazaki
Toshiaki
T
Kikuchi
Ichiro
I
Sora
Motoaki
M
Takayanagi
Hirohito
H
Kita
Isao
I
Ohno
D000818:Animals; D001249:Asthma / Q000276:immunology* / Q000503:physiopathology / Q000523:psychology*; D016535:Bronchial Hyperreactivity / Q000503:physiopathology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology / Q000276:immunology; D003345:Corticosterone / Q000097:blood / Q000276:immunology / Q000494:pharmacology; D004195:Disease Models, Animal; D005260:Female; D005938:Glucocorticoids / Q000097:blood* / Q000276:immunology / Q000494:pharmacology; D007249:Inflammation / Q000523:psychology; D018664:Interleukin-12 / Q000276:immunology; D018793:Interleukin-13 / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D015735:Mifepristone / Q000494:pharmacology; D011965:Receptors, Glucocorticoid / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D012137:Respiratory System / Q000503:physiopathology; D012737:Sex Factors; D013315:Stress, Psychological / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
D005938:Glucocorticoids; D018793:Interleukin-13; D011965:Receptors, Glucocorticoid; D018664:Interleukin-12; D015735:Mifepristone; D003345:Corticosterone