CRH and the immune system

Inflammatory cytokines released during immune system activation can stimulate the hypothalamic-pituitary-adrenal axis and cause increased secretion of corticotropin-releasing hormone (CRH), adrenocorticotropin and glucocorticoids. Identification of CRH peptide and mRNA, as well as its receptors in immune tissues, suggested a role for this peptide as a mediator of the neuroendocrine-immune interactions. Experimental evidence suggests that CRH may modulate the immune and inflammatory responses via two pathways: an antiinflammatory one operated by centrally released CRH, most likely through stimulation of glucocorticoid and catecholamine release, and one proinflammatory, through direct action of peripherally released CRH. This review highlights these concepts. In addition preliminary data on immune activation and inflammatory response in CRH-deficient mice created in our laboratory are discussed.