Neuroendocrine Immunoregulation in Multiple Sclerosis

Table 1

Neuroendocrine factors and their immunomodulatory effects.

Substance	Receptor	Effect on immune response	Reference
Acetylcholine	Muscarinic acetylcholine receptor (mAChR)	Differentiating towards a Th1 phenotype	[111]
	Nicotinic acetylcholine receptor (nAChR)	Inhibits IL-1β, IL-6, IL-18, and TNF-α production	[109]
ACTH	ACTH receptor	Inhibits IFN-γ production and Ig production and blocks macrophage activation by IFN-γ	[231]
Adrenalin/; noradrenalin	α-Adrenergic receptors	Upregulation of cAMP; inhibits IL-1, IL-6, IL-12, and TNF-α production; enhances IL-10 production	[91]
	β-Adrenergic receptors	Downregulation of cAMP	[93, 94]
Cortisol	Glucocorticoid receptor (GR)	Inhibits IFN-γ, IL-2, IL-6, and TNF-α; Enhances IL-4 and TGF-β production; Enhances immune cell expression of IL-1, IL-2, IL-6, and IFN-γ receptors	[10, 232, 233]
CRH	Corticotropin-releasing hormone receptor	Activates macrophages; Inhibits IL-1 and IL-6 production	[231]
Dopamine	D1-like receptors	Upregulation of cAMP	[99]
	D2-like receptors	Downregulation of cAMP	[99]
GABA	GABA receptors	Reduces the proliferative response of activated CD8^+ T cells; Reduces IL-6 release	[169, 170]
Glutamate	mGluR1	Enhances IL-2, IL-6, IL-10, TNF-α, and IFN-γ production	[116]
	mGluR5	Inhibits IL-6 production	[116]
Growth hormone	Growth hormone receptor	Activates macrophages and enhances H2O2 production	[234]
Gonadotropin-releasing hormone	Gonadotropin-releasing hormone receptor	Increases IL2R expression, T- and B-cell proliferation, and serum Ig	[235, 236]
Histamine	Histamine 1 receptor, histamine 4 receptor	Enhances IL-1β, IL-6, IL-8, and RANTES production; Induce chemotaxis of CD4^+ T cells	[152–154]
	Histamine 2 receptor	Inhibits IL-12, IFN-γ and TNF-α, and enhances IL-10 production	[155]
Luteinizing hormone	Luteinizing hormone/choriogonadotropin receptor	Enhances IL-2 stimulated T-cell proliferation	[237]
Melatonin	Melatonin receptor	Enhances IL-1, IL-2, IL-6, and IFN-γ production	[238, 239]
Neurokinin A	Neurokinin 2 receptor (NK2-receptor)	Enhances mRNA expression of IFN-α and IFN-β; Enhances DC function	[138]
Estrogen	Estrogen receptor	Enhances T-cell proliferation and activity IFN-γ gene promotor	[240]
Progesterone	Progesterone receptor	Enhances IL-4 production and CD30 expression	[85, 86]
Prolactin	Prolactin receptor	Enhances T cell proliferation, IFN-γ, IL-2 receptor expression, and macrophage function	[42, 43]
Serotonin	Serotonin-1a receptor	Enhances NK cell cytotoxicity; Downregulation of cAMP; Stimulation of T-cell proliferation	[142, 143]
	Serotonin-2a receptor	Inhibits lymphocyte proliferation	[144]
Substance P	Neurokinin 1 receptor (NK1-receptor)	Enhances IL-1β, IL-6, TNF-α, MIP-1β, and IFN-γ production; Enhances T-cell proliferation; Enhances NK cell cytotoxicity	[129, 130, 132]
Vasopressin	Vasopressin receptor	Enhances IFN-γ production	[241]
VIP	Vasoactive intestinal peptide receptor	Inhibits T-cell proliferation and IL-12; Enhances IL-5 and cAMP production	[242]