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 disease. 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.