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Stress, Corticotropin‐Releasing Hormone, Glucocorticoids, and the Immune/Inflammatory Response: Acute and Chronic Effects a
Author(s) -
ELENKOV ILIA J.,
WEBSTER ELIZABETH L.,
TORPY DAVID J.,
CHROUSOS GEORGE P.
Publication year - 1999
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.1999.tb07618.x
Subject(s) - corticotropin releasing hormone , immune system , endocrinology , histamine , medicine , inflammation , proinflammatory cytokine , tumor necrosis factor alpha , hormone , immunology
A bstract : 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.