Early-life psychological stress exacerbates adult mouse asthma via the hypothalamus-pituitary-adrenal axis.
BACKGROUND
Despite accumulating evidence that psychological stress has a short-lasting detrimental effect on asthma, little is known about the way stress in childhood predisposes to adult asthma.


OBJECTIVE
Using a communication box, we investigated the long-lasting effect of early psychological and physical stress on adult asthma in mice.


METHODS
Male BALB/c mice were exposed to either psychological stress or physical stress three times (every other day) during their fourth week of life. The mice were sensitized to ovalbumin at 8 and 10 weeks, and an ovalbumin airway challenge was conducted at the age of 11 weeks.


RESULTS
Twenty-four hours after ovalbumin challenge, both psychological and physical stress-exposed mice exhibited a significant acceleration in the number of total mononuclear cells and eosinophils and airway hyperresponsiveness compared with control mice. No differences in serum anti-OVA-specific immunoglobulin E levels were found between stress-exposed and control animals after antigen sensitization. In the psychological stress group, but not in the physical stress group, an elevation of the serum corticosterone levels during ovalbumin challenge was significantly attenuated in comparison with the control group. Moreover, pretreatment with RU-486, a glucocorticoid receptor antagonist, before ovalbumin challenge completely inhibited a psychological stress-induced exacerbation of asthma. However, pretreatment with GR-82334, a neurokinin-1 receptor antagonist, failed to affect physical stress-induced augmentation of airway inflammation.


CONCLUSIONS
Early psychological and physical stresses aggravated adult asthma via hyporesponsiveness of the hypothalamic-pituitary-adrenal axis during antigen challenge and via a pathway(s) distinct from the hypothalamic-pituitary-adrenal axis or neurokinin-1 receptors.
Chida
Yoichi
Y
Department of Psychosomatic Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Sudo
Nobuyuki
N
Sonoda
Junko
J
Hiramoto
Tetsuya
T
Kubo
Chiharu
C
D000818:Animals; D001249:Asthma / Q000378:metabolism / Q000503:physiopathology* / Q000517:prevention & control; D001985:Bronchial Provocation Tests; D001992:Bronchoalveolar Lavage Fluid; D003345:Corticosterone / Q000097:blood; D004804:Eosinophils / Q000378:metabolism; D006727:Hormone Antagonists / Q000494:pharmacology; D007030:Hypothalamo-Hypophyseal System / Q000503:physiopathology*; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D015735:Mifepristone / Q000494:pharmacology; D064729:Neurokinin-1 Receptor Antagonists; D018377:Neurotransmitter Agents / Q000494:pharmacology; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D010803:Physalaemin / Q000031:analogs & derivatives / Q000494:pharmacology; D010913:Pituitary-Adrenal System / Q000503:physiopathology*; D011965:Receptors, Glucocorticoid / Q000037:antagonists & inhibitors; D013312:Stress, Physiological / Q000503:physiopathology*; D013315:Stress, Psychological / Q000503:physiopathology*
D006727:Hormone Antagonists; D064729:Neurokinin-1 Receptor Antagonists; D018377:Neurotransmitter Agents; D011965:Receptors, Glucocorticoid; C079014:GR 82334; D010803:Physalaemin; D015735:Mifepristone; D010047:Ovalbumin; D003345:Corticosterone