THE ROLE OF CORTICOTROPIN-RELEASING HORMONE IN NEUROENDOCRINE-IMMUNE INTERACTIONS

Neuroendocrine-immune interactions are profoundly regulated by cortico tropin-releasing hormone (CRH) indirectly, through activation of a glo bal stress response, and directly, through pro-inflammatory actions on peripheral immune functions. The indirect effects of stress on immune /inflammatory responses occur via the stress-induced activation of the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic/adrenom edullary system. We have demonstrated that glucocorticoids and catecho lamines favor T helper 2 (TH2) over T helper 1 (TH1) immune cells and mediators, by controlling the production of specific key regulatory cy tokines. This could explain the influences of chronic stress on the de velopment, course, and pathology of certain allergic, autoimmune/infla mmatory, infectious, and neoplastic diseases. We have also shown that 'immune CRH' is secreted peripherally and plays a direct immunomodulat ory role as an autocrine or paracrine mediator of inflammation. Upon r elease from immune cells and peripheral sensory afferent and/or postga nglionic sympathetic nerves, CRH acts locally to elicit pro-inflammato ry responses. This would explain the triggering or exacerbation of cer tain allergic or vasokinetic states by acute stress.