The Role of the Sympathetic Nervous System in the Modulation of Immune Responses

Abstract

Studies of the effects of sympathectomy on immune responses invariably suggest that norepinephrine (NE) and the sympathetic nervous system have important roles in modulation of immune responses. Lymphoid organs, both primary and secondary, are innervated by NE-containing postganglionic sympathetic nerve fibers, as well as a variety of peptidergic fibers. At the light microscopic level, much of the innervation appears to be associated with the vasculature in these organs, although there are always fibers that appear to have no anatomic relationship to blood vessels. Immunocytochemistry of the rodent spleen at the ultrastructural level, using antibodies for tyrosine hydroxylase, has revealed that, in addition to abundant blood vessel and trabecular smooth-muscle innervation, there is direct contact between tyrosine hydroxylase-positive nerve terminals and both lymphocytes and macrophages. The presence of sympathetic nerve terminals near, or in direct contact with, lymphocytes in lymphoid organs, including thymus, spleen, lymph nodes, and bone marrow, and the presence of adrenergic receptors on lymphocytes suggest that sympathetic innervation and the transmitter NE may be important in the modulation of immune responses. Not only does NE affect cytokine production, but it is also likely that some cytokines also regulate NE release both via central nervous system sympathetic responses to circulating cytokines and by interactions with local noradrenergic nerve terminals innervating lymphoid organs and other peripheral target sites where inflammation or immune responses take place.