A role for CRH and the sympathetic nervous system in stress-induced immunosuppression

Central CRH coordination of the behavioral and physiologic sequelae of stress has been well established, and so it is parsimonious to suggest that CRH might also coordinate the immunologic sequelae. The studies presented here lend support to this suggestion. CRH administration into the brain was shown to modulate aspects of both cellular and humoral immune function, and the inhibition of CRH release in the brain following stress inhibited stress-associated immunosuppression. The effects of CRH appear to be mediated by the sympathetic branch of the autonomic nervous system, as chemical sympathectomy and pharmacological blockade of beta-adrenergic receptors both reversed the effects of CRH on immune function. In contrast, removal of the adrenal glands did not alter the immunologic effects of CRH. These links among CRH in the brain, sympathetic activation, and immune function suggest the possibility that immune function may be altered in other conditions characterized by elevated sympathetic tone, such as depression and aging, and that these alterations may be attributed to CRH dysregulation in the brain. These studies shed light on the intricate relationship between the brain and the immune system, and also illuminate its complexity. The differential regulation of CRH in the brain and the periphery is one example of the latter. These findings also set the stage for potential clinical intervention with CRH antagonists, for example, to treat compromised immune function associated with chronic stress, depression, or aging.