Adrenergic regulation of immune cell function and inflammation

Abstract

The sympathetic nervous system integrates the functions of multiple organ systems by regulating their autonomic physiological activities. The immune system is regulated both locally and systemically by the neurotransmitters epinephrine and norepinephrine secreted by the adrenal gland and local sympathetic neurons. Immune cells respond by activation of adrenergic receptors, primarily the β2-adrenergic receptor, which signal through heterotrimeric G-proteins. Depending upon the cell type, adrenergic signaling regulates a variety of functions in immune cells ranging from cellular migration to cytokine secretion. Furthermore, due to the diurnal oscillation of systemic norepinephrine levels, various immune functions follow a circadian rhythmic pattern. This review will highlight recent advances in our understanding of how the sympathetic nervous system regulates both innate and adaptive immune functions and how this regulation is linked to circadian rhythms.

Neurotransmitter System-Targeting Drugs Antagonize Growth of the Q Fever Agent, Coxiella burnetii, in Human Cells

“…For example, 5-HT impacts alveolar macrophage production of tumor necrosis factor alpha (TNF-α) and interleukin-10 (IL-10) ( 42 ), which are involved in proinflammatory and anti-inflammatory responses, respectively. In addition, norepinephrine signaling through β 2 -adrenergic receptors may drive macrophage IL-10 production ( 43 ). C. burnetii triggers a robust human macrophage inflammatory response characterized by production of TNF-α, IL-6, and IL-8, and the pathogen stimulates anti-inflammatory IL-10 production ( 3 , 29 ).…”

“…For example, resolvin and clavanin modulate immune responses to Escherichia coli and Staphylococcus aureus , indicating that dampening the host inflammatory response prevents robust bacterial growth, effectively inhibiting disease progression ( 46 – 48 ). Moreover, neurotransmitter receptor expression and signaling impacts macrophage polarization that defines the inflammatory state of the cell ( 43 , 49 ). C. burnetii promotes alveolar macrophage transition from M1 to M2 polarization to provide a more hospitable growth niche ( 3 ), and 5-HT, dopamine, or norepinephrine signaling may contribute to this event.…”

Endocrine Manifestations of Systemic Lupus Erythematosus

“…Its effects are mediated by noradrenaline which acts through the relevant receptors [37]. Noradrenaline receptors are expressed by immune cells, namely T and B lymphocytes and macrophages [38]. Noradrenaline and adrenaline stimulate IL-10 and transforming growth factor-b production, thus enhancing Th2 immunity [39,40].…”

A good gut feeling on Sarm1-mediated axon degeneration

“…These data suggest that the preservation of catecholaminergic axons in Sarm1 knockout mice enhances colon inflammation through sustained norepinephrine release, promoting IL-17A and IL-17F expression in nearby immune cells. It will be important to elucidate how norepinephrine, a well-known immunosuppressive agent (Sharma and Farrar, 2020 ), regulates these novel pro-inflammatory transcriptional changes in immune cells in future studies.…”