title: Blockade of mineralocorticoid receptors enhances naïve T-helper cell counts during early sleep in humans.
abstract: Sleep supports the formation of immunological memory as evidenced by a stronger immune response to vaccination if subjects sleep during the subsequent night than if they stay awake. One mechanism underlying this adjuvant-like action of sleep might be an enhanced homing of circulating naïve T cells to lymph nodes. Indeed, compared to nocturnal wakefulness, sleep acutely lowers T cell counts in peripheral blood during the early night, with the efflux of these cells to lymphoid tissues possibly mediated by sleep-associated release of the mineralocorticoid aldosterone. We show here that blocking mineralocorticoid receptors by spironolactone (200mg, orally at 23:00 h and again at 4:00 h) in 11 healthy men enhances naïve T-helper cell counts in blood during early nocturnal sleep. Effects in the same direction on naïve cytotoxic T cells and central memory T-helper cells were less consistent. Spironolactone did not influence T cell subsets not migrating to lymph nodes (i.e., CD62L(-) effector memory and effector T cells), or expression of CD62L and CXCR4. The typical circadian decrease in T cell numbers in the morning hours was not affected by the blockade of mineralocorticoid receptors, in line with the view that this decrease is mainly due to activation of glucocorticoid receptors during the circadian morning rise in cortisol. We assume that sleep-associated activation of mineralocorticoid receptors at a time of low cortisol levels contributes to an enhanced redistribution of circulating naïve T-helper cells to lymph nodes, as a mechanism that eventually promotes immunological memory formation.
authors.affiliation: Department of Neuroendocrinology, University of Lübeck, Lübeck, Germany.
authors.forename: Luciana
authors.initials: L
authors.lastname: Besedovsky
authors.forename: Jan
authors.initials: J
authors.lastname: Born
authors.forename: Tanja
authors.initials: T
authors.lastname: Lange
mesh_terms: D000293:Adolescent; D000328:Adult; D000450:Aldosterone / Q000502:physiology; D001794:Blood Pressure / Q000502:physiology; D002465:Cell Movement / Q000187:drug effects; D004311:Double-Blind Method; D006728:Hormones / Q000097:blood; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D019041:L-Selectin / Q000378:metabolism; D018655:Lymphocyte Count; D008297:Male; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology; D017286:Polysomnography; D019718:Receptors, CXCR4 / Q000378:metabolism; D018161:Receptors, Mineralocorticoid / Q000187:drug effects*; D012890:Sleep / Q000276:immunology*; D012894:Sleep Stages; D013148:Spironolactone / Q000494:pharmacology; D006377:T-Lymphocytes, Helper-Inducer / Q000502:physiology*; D055815:Young Adult
chemical_list: D006728:Hormones; D000451:Mineralocorticoid Receptor Antagonists; D019718:Receptors, CXCR4; D018161:Receptors, Mineralocorticoid; D019041:L-Selectin; D013148:Spironolactone; D000450:Aldosterone; D006854:Hydrocortisone