The involvement of micro-opioid receptors in the central nervous system in the worsening of allergic airway inflammation by psychological stress in mice.
BACKGROUND
Psychological stress has a recognized association with asthma symptoms. However, the mechanisms linking stress to the exacerbation of asthma are not well defined. mu-Opioid receptors (MOR) have been shown to be involved in the shift of the immune system toward a Th2-predominant response caused by psychological stress.


OBJECTIVE
To test the hypothesis that MOR play a role in the worsening of allergic airway inflammation evoked by psychological stress.


METHODS
Sensitized mice were exposed to restraint stress followed by antigen challenge. The levels of corticosterone and ovalbumin (OVA)-specific IgE in the blood and the levels of inflammatory cells and cytokine contents in bronchoalveolar lavage fluid were compared between stressed and nonstressed mice. The effects of MOR gene deletion and MOR antagonists/agonists were also investigated.


RESULTS
Stress exposure was confirmed by an increase in corticosterone levels. Although OVA-specific IgE levels were not significantly different, the numbers of inflammatory cells and Th2 cytokine levels after antigen challenge in stressed mice were significantly higher than in nonstressed mice. MOR gene deletion ameliorated the stress-induced worsening of antigen-induced airway inflammation, and the administration of morphine, a MOR agonist, reproduced the stress-induced antigen-induced airway inflammation. Selective blocking of MOR in the central nervous system (CNS) significantly reduced stress-induced inflammatory exacerbation, but the blocking of peripheral MOR did not.


CONCLUSIONS
MOR in the CNS are involved in psychological stress-induced aggravation of allergic airway inflammation.
Okuyama
Kaori
K
Department of Pathophysiology, Tohoku Pharmaceutical University, Sendai, Japan.
Wada
Kana
K
Sakurada
Shinobu
S
Mizoguchi
Hirokazu
H
Komatsu
Hiroshi
H
Sora
Ichiro
I
Tamura
Gen
G
Ohkawara
Yuichi
Y
Takayanagi
Motoaki
M
Ohno
Isao
I
D000818:Animals; D001249:Asthma / Q000150:complications / Q000276:immunology / Q000523:psychology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology / Q000276:immunology; D002490:Central Nervous System / Q000378:metabolism*; D016207:Cytokines / Q000032:analysis; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009020:Morphine / Q000494:pharmacology; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D017450:Receptors, Opioid, mu / Q000819:agonists / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D013315:Stress, Psychological / Q000150:complications / Q000276:immunology / Q000523:psychology; D018418:Th2 Cells / Q000276:immunology*
D016207:Cytokines; D009292:Narcotic Antagonists; D017450:Receptors, Opioid, mu; D007073:Immunoglobulin E; D009271:Naltrexone; C024524:beta-funaltrexamine; D009020:Morphine