Contribution of stress to asthma worsening through mast cell activation.
OBJECTIVE
To review the available evidence linking stress to asthma and to investigate whether mast cells contribute to the effect of stress through activation by corticotropin-releasing hormone (CRH).


METHODS
The PubMed database was searched for articles (1998-2011) using the keywords anxiety, asthma, exacerbation, inflammation, mast cells, socioeconomic status, stress, violence, and worsening.


METHODS
Articles were selected based on their relevance to the topic, with emphasis on clinical or epidemiologic data linking stress to asthma and studies that offered possible explanations for how stress may affect asthma.


RESULTS
Many articles point to an association between stress (socioeconomic status, interpersonal conflicts, emotional distress, terrorism) and asthma exacerbations but without any distinct pathogenetic mechanism. A few articles have reported reduced circulating cortisol and/or sensitivity to corticosteroids. We propose that mast cells, known to be involved in the pathophysiology of asthma, can be activated by CRH, which is secreted under stress in the lungs, leading to selective release of proinflammatory mediators. This effect may be augmented by neuropeptides or cytokines. CRH also reduces T-regulatory cell production of interleukin 10, which in known to inhibit allergic mast cell activation.


CONCLUSIONS
More studies are required to investigate lung levels of CRH and selective mast cell mediators. Reducing stress and using CRH receptor antagonists and/or mast cell blockers may serve as possible new therapeutic approaches for asthma.
Molecular Immunopharmacology and Drug Discovery Laboratory, Department of Molecular Physiology and Pharmacology, Tufts University School of Medicine, Tufts Medical Center, Boston, MA 02111, USA. theoharis.theoharides@tufts.edu
Theoharis C
TC
Theoharides
Souad
S
Enakuaa
Nikolaos
N
Sismanopoulos
Shahrzad
S
Asadi
Evangelos C
EC
Papadimas
Asimenia
A
Angelidou
Konstantinos-Dionysios
KD
Alysandratos
D000293:Adolescent; D000328:Adult; D001249:Asthma / Q000209:etiology / Q000276:immunology* / Q000628:therapy; D002648:Child; D002675:Child, Preschool; D003346:Corticotropin-Releasing Hormone / Q000032:analysis / Q000276:immunology* / Q000378:metabolism*; D005260:Female; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology; D016753:Interleukin-10 / Q000276:immunology / Q000378:metabolism; D008168:Lung / Q000737:chemistry; D008297:Male; D008407:Mast Cells / Q000276:immunology* / Q000378:metabolism; D009479:Neuropeptides / Q000276:immunology / Q000378:metabolism; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors; D013315:Stress, Psychological / Q000150:complications / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism
D009479:Neuropeptides; D018019:Receptors, Corticotropin-Releasing Hormone; D016753:Interleukin-10; D003346:Corticotropin-Releasing Hormone