Fundamental Aspects of Neural-Immune Signaling

Abstract

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.

Sympathetic activation and inflammatory response in patients with subarachnoid haemorrhage

“…While a number of studies indicate that catecholamines participate in cytokine production [1,2,3,4,5,6,7,8,9,10,11,12], we found no evidence of a quantitative link between the degree of sympathetic nervous activation and the magnitude of the inflammatory response during a period of 10 days after SAH.…”

“…Emerging evidence indicates that the sympathetic nervous system, through its innervation of lymphoid organs, can modulate the inflammatory response [1,2,3,4,5,6,7].…”

“…Research over the past 20 years suggests that norepinephrine (NE) fulfils the criteria for neurotransmittor/neuromodulator in lymphoid organs [5,6]. There are conflicting data whether NE, the principal neurotransmitter of the sympathetic nervous system, has immunostimulatory or immunosuppressive effects [1,7,8,9,10,11].…”

Molecular Basis of Neuroimmune Interaction in an In Vitro Coculture Approach

“…Immunohistochemical studies show that there is the innervation of both primary and secondary lymphoid organs with sympathetic nerve fibers (10,11,(37)(38)(39), and that mast cells are also often found in the proximity of nerve fibers containing neuropeptides in a variety of tissues including skin, intestine, and dura mater (34,(40)(41)(42). Based on electron microscopic observation, nerve terminals are in direct apposition to T cells and mast cells.…”

“…Sympathetic nerve fibers innervate the vasculature and parenchyma of primary and secondary lymphoid organs, and other lymphoid tissues (10,11). Immunohistochemical studies demonstrated a close association of sympathetic nerve terminals with macrophages and lymphocytes.…”