Fundamental aspects of neural-immune signaling.

Noradrenergic and peptidergic nerve fibers abundantly innervate the parenchyma of both primary (bone marrow) and secondary (spleen, lymph nodes) lymphoid organs. Nerve fibers distribute within the parenchyma of these organs, as well as along smooth muscle compartments. Both noradrenaline and peptides such as substance P have been shown to fulfill the basic criteria for neurotransmission with lymphocytes, macrophages, and other immunocytes as targets. Denervation or pharmacological manipulation of these neurotransmitters can profoundly alter immunological reactivity at the individual cellular level, at the level of complex multicellular interactions (such as antibody response), and at the level of host response to a disease-producing challenge. The characteristic and mechanisms of bidirectional neural-immune signaling may provide a novel approach to immunologically-mediated disease, both pharmacologically and behaviorally.