Stress, Corticotropin-Releasing Hormone, Glucocorticoids, and the Immune/Inflammatory Response: Acute and Chronic Effectsa

Authors

  • ILIA J. ELENKOV,

    1. Pediatric Endocrinology Section, Developmental Endocrinology Branch, National Institute of Child Health and Human Development, Bethesda, Maryland 20892, USA
    2. Inflammatory Joint Diseases Section, Arthritis and Rheumatism Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
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  • ELIZABETH L. WEBSTER,

    1. Pediatric Endocrinology Section, Developmental Endocrinology Branch, National Institute of Child Health and Human Development, Bethesda, Maryland 20892, USA
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  • DAVID J. TORPY,

    1. Pediatric Endocrinology Section, Developmental Endocrinology Branch, National Institute of Child Health and Human Development, Bethesda, Maryland 20892, USA
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  • GEORGE P. CHROUSOS

    Corresponding author
    1. Pediatric Endocrinology Section, Developmental Endocrinology Branch, National Institute of Child Health and Human Development, Bethesda, Maryland 20892, USA
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  • a

    An earlier version of this manuscript was published in Ann. N. Y. Acad. Sci. 840: 21–32.

Address correspondence to Dr. George P. Chrousos, Pediatric Endocrinology Section, DEB, NICHD, Building 10, Room 10N262, NIH, Bethesda, MD 20892. Tel: (301) 496–5800; fax: (301) 402–0574; e-mail: chrousosg@nichd.nih.gov

Abstract

Abstract: Corticotropin-releasing hormone (CRH) influences the immune system indirectly, through activation of the hypothalamic-pituitary-adrenal axis and sympathetic system, and directly, through local modulatory actions of peripheral (immune) CRH. We recently demonstrated that catecholamines and histamine potently inhibited interleukin (IL)-12 and stimulated IL-10, whereas glucocorticoids suppressed IL-12, but did not affect IL-10 production ex vivo. Thus, both glucocorticoids and catecholamines, the end products of the stress system, and histamine, a product of activated mast cells, may selectively suppress cellular immunity and favor humoral immune responses. We localized immunoreactive CRH in experimental carrageenin-induced aseptic inflammation and, in humans, in inflamed tissues from patients with several autoimmune diseases. In addition, we demonstrated that CRH activated mast cells via a CRH receptor type 1-dependent mechanism, leading to release of histamine and hence vasodilatation and increased vascular permeability. Thus, activation of the stress system, through direct and indirect effects of CRH, may influence the susceptibility of an individual to certain autoimmune, allergic, infectious or neoplastic diseases. Antalarmin, a novel nonpeptide CRH antagonist, prevented several proinflammatory effects of CRH, thus revealing its therapeutic potential in some forms of inflammation.

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