Adrenergic regulation of innate immunity: a review

Abstract

The sympathetic nervous system has a major role in the brain-immune cross-talk, but few information exist on the sympathoadrenergic regulation of innate immune system. The aim of this review is to summarize available knowledge regarding the sympathetic modulation of the innate immune response, providing a rational background for the possible repurposing of adrenergic drugs as immunomodulating agents. The cells of immune system express adrenoceptors (AR), which represent the target for noradrenaline and adrenaline. In human neutrophils, adrenaline and noradrenaline inhibit migration, CD11b/CD18 expression, and oxidative metabolism, possibly through β-AR, although the role of α1- and α2-AR requires further investigation. Natural Killer express β-AR, which are usually inhibitory. Monocytes express β-AR and their activation is usually antiinflammatory. On murine Dentritic cells (DC), β-AR mediate sympathetic influence on DC-T cells interactions. In human DC β2-AR may affect Th1/2 differentiation of CD4+ T cells. In microglia and in astrocytes, β2-AR dysregulation may contribute to neuroinflammation in autoimmune and neurodegenerative disease. In conclusion, extensive evidence supports a critical role for adrenergic mechanisms in the regulation of innate immunity, in peripheral tissues as well as in the CNS. Sympathoadrenergic pathways in the innate immune system may represent novel antiinflammatory and immunomodulating targets with significant therapeutic potential.

Polycystic ovary syndrome and circulating inflammatory markers

“…''Sympatho-adrenergic pathways in the innate immune system may represent novel antiinflammatory and immune-modulating targets with significant therapeutic potential'' (48). The crosstalk between two super systems is clear but in PCOS women the role of NA in mediating inflammatory responses is less clear, with evidence of both pro-and antiinflammatory effects.…”

A targeted genome association study examining transient receptor potential ion channels, acetylcholine receptors, and adrenergic receptors in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis

“…This is required for vasoconstriction of blood vessels throughout the body including the skin, gastrointestinal system, genitourinary system, kidney and brain. It is also involved in the glycogenolysis and gluconeogenesis of adipose tissue in the liver, in addition to enabling secretions from sweat glands [26–29]. These above processes have been associated with symptomatology of CFS/ME [3, 4].…”

Predictors of Subclinical Inflammatory Obesity: Plasma Levels of Leptin, Very Low-Density Lipoprotein Cholesterol and CD14 Expression of CD16+ Monocytes

“…Our work also suggests that CA such as AD and NA have an immunomodulatory role in obesity. The adrenergic regulation of human monocytes was recently reviewed [47]. On human monocytes, even if under certain conditions pro-inflammatory responses may arise, the predominant view is that β-adrenoceptor (β-AR) activation is usually anti-inflammatory and immunosuppressive.…”