title: Sleep associated regulation of T helper 1/T helper 2 cytokine balance in humans.
abstract: Recent human studies suggested a supportive influence of regular nocturnal sleep on immune responses to experimental infection (vaccination). We hypothesized here that sleep could ease such responses by shifting the balance between T helper 1 (Th1) and T helper 2 (Th2) cytokine activity towards Th1 dominance thereby favoring cellular over humoral responses to infection. We compared the Th1/Th2 cytokine balance in 14 healthy men during regular nocturnal sleep (between 23:00 and 07:00 h) and while remaining awake during the same nocturnal interval, in a within-subject cross-over design. Blood was collected every 2 h. Production of T cell derived cytokines--interferon-gamma (IFN-gamma), interleukin-2 (IL-2), interleukin-4 (IL-4), and tumor necrosis factor-alpha (TNF-alpha)--was measured at the single cell level using multiparametric flow cytometry. Also, several immunoactive hormones--prolactin, growth hormone (GH), thyroid stimulating hormone (TSH), cortisol, and melatonin--were measured, the release of which is known to be regulated by sleep. Compared with wakefulness, early nocturnal sleep induced a shift in the Th1/Th2 cytokine balance towards increased Th1 activity, as indicated by an increased (p <.05) ratio of IFN-gamma/IL-4 producing T helper cells. However, the Th1 shift was only of moderate size and replaced by Th2 dominance during late sleep (p <.05). It could be mediated via release of prolactin and GH which both were distinctly increased during sleep (p <.001). Though unexpected, the most pronounced effect of sleep on T cell cytokine production was a robust decrease in TNF-alpha producing CD8+ cells probably reflecting increased extravasation of cytotoxic effector and memory T cells.
authors.affiliation: Department of Neuroendocrinology, University of Lübeck, Ratzeburger Allee 160, Haus 23a, 23538 Lübeck, Germany.
authors.forename: Stoyan
authors.initials: S
authors.lastname: Dimitrov
authors.forename: Tanja
authors.initials: T
authors.lastname: Lange
authors.forename: Swantje
authors.initials: S
authors.lastname: Tieken
authors.forename: Horst L
authors.initials: HL
authors.lastname: Fehm
authors.forename: Jan
authors.initials: J
authors.lastname: Born
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D002940:Circadian Rhythm; D018592:Cross-Over Studies; D005434:Flow Cytometry; D019382:Human Growth Hormone / Q000097:blood; D006801:Humans; D007371:Interferon-gamma / Q000097:blood; D007376:Interleukin-2 / Q000097:blood; D015847:Interleukin-4 / Q000097:blood; D018655:Lymphocyte Count; D008297:Male; D011388:Prolactin / Q000097:blood; D012016:Reference Values; D012890:Sleep / Q000276:immunology* / Q000502:physiology; D012892:Sleep Deprivation / Q000097:blood / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000502:physiology; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D013972:Thyrotropin / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D014851:Wakefulness / Q000502:physiology
chemical_list: D007376:Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D019382:Human Growth Hormone; D015847:Interleukin-4; D007371:Interferon-gamma; D011388:Prolactin; D013972:Thyrotropin