Regulation of the immune system by sympathetic neural mechanisms

The immune system is made up of primary and secondary lymphoid organs, containing lymphocytes and several accessory cell types, which are the key agents of immunological reactivity. Some of the basic features of immune responses are reviewed. Several pathways from the CNS to the immune system are of potential importance in physiological regulation. The sympathetic nervous system innervates all lymphoid organs with noradrenergic fibers. Furthermore, lymphocytes have receptors for sympathetic neurotransmitters, e.g., beta adrenoceptors. Sympathetic denervation by pharmacologic treatment with 6-hydroxydopamine has a marked affect on several immune responses, including antibody production, delayed hypersensitivity, and generation of cytotoxic T lymphocytes. Norepinephrine, epinephrine, and synthetic adrenergic agonists potentiate cytotoxic T lymphocyte responses in vitro. This appears to be mediated via beta 2 adrenoceptors. Studies with adrenoceptor blockers also indicate a possible role for alpha receptors. In sum, our studies indicate that intact noradrenergic innervation is required for normal immune function. Sympathetic neural influence, via norepinephrine release, may be exerted at the cellular (activation, proliferation, secretion of products) as well as the physiologic (antigen localization, lymphocyte migration) levels.