Dopamine and norepinephrine are embracing their immune side and so should we

Abstract

While the history of neuroimmunology is long, the explicit study of neuroimmune communication, and particularly the role of catecholamines in neuroimmunity, is still emerging. Recent studies have shown that catecholamines, norepinephrine, epinephrine, and dopamine, are central to multiple complex mechanisms regulating immune function. These studies show that catecholamines can be released from both the nervous system and directly from immune cells, mediating both autocrine and paracrine signaling. This commentary highlights the importance of catecholaminergic immunomodulation and discusses new considerations needed to study the role of catecholamines in immune homeostasis to best leverage their contribution to disease processes for the development of new therapeutic approaches.

Figure 1. Sources and effects of catecholamines in immune regulation.

Catecholamines are generated from a variety of cell types in both the CNS and periphery and have been shown to mediate a multitude of immune functions. Only some of these sources and immunoregulatory effects are represented here. (1) In the CNS, released catecholamines facilitate bidirectional interactions between catecholaminergic neurons and CNS immune cells, such as microglia, that can modulate neuronal function and shape behavior. (2) In the periphery, catecholamine levels can be regulated by direct and indirect interaction with the vagus nerve, inducing changes in immune function, such as the cholinergic inflammatory reflex, in multiple organ systems. (3) Indirect changes in response to vagal stimulation are often mediated by production of catecholamines in non-immune cells, such as enterochromaffin cells or immune cells themselves. These effects can also occur in response to other stimuli. (4) Interaction with catecholamines drives autocrine and paracrine signaling within and between immune populations, regulating multiple immune functions in multiple types of immune cells.