title: Sleep-like concentrations of growth hormone and cortisol modulate type1 and type2 in-vitro cytokine production in human T cells.
abstract: Slow wave sleep (SWS) is characterized by maximum release of growth hormone (GH) and minimum release of cortisol. We hypothesized that this hormonal pattern during SWS leads, in addition to generally increased T cell cytokine production, to a shift towards type1 cytokines. To test this hypothesis, blood was sampled from 8 humans during SWS, and whole blood cultures were activated in-vitro with ionomycin and phorbol-myrestate-acetate (PMA) in the absence and presence of GH neutralizing antibody (Ab) or physiological concentrations of cortisol. Production of interferon-gamma (IFN-gamma), interleukin-2 (IL-2), IL-4, and tumor necrosis factor-alpha (TNF-alpha) was measured using multiparametric flow cytometry. GH Ab decreased IFN-gamma+CD4+ cells but had no effect on other cytokines. Cortisol alone and in combination with GH Ab decreased CD4+ and CD8+ cells producing IFN-gamma, TNF-alpha and IL-2. Simultaneously, these two reactants reduced IL-4+CD4+ cells, so that the ratio of IFN-gamma/IL4 producing CD4+ cells indicated an unexpected shift towards type1 dominance. Results support the view that release of GH by increasing particularly production of IFN-gamma can contribute to the shift in type1/type2 balance towards type1 activity characterizing SWS. Suppression of cortisol during this sleep period enhances both type1 and type2 activity. Yet, our finding of predominant type1 activity after cortisol administration, rules out any relevance of this suppression for the shift towards type1 activity during SWS.
authors.affiliation: Department of Internal Medicine, University of Lübeck, Germany.
authors.forename: Tanja
authors.initials: T
authors.lastname: Lange
authors.forename: Stoyan
authors.initials: S
authors.lastname: Dimitrov
authors.forename: Horst-Lorenz
authors.initials: HL
authors.lastname: Fehm
authors.forename: Jan
authors.initials: J
authors.lastname: Born
mesh_terms: D000328:Adult; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis*; D005434:Flow Cytometry; D013006:Growth Hormone / Q000494:pharmacology*; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology*; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000494:pharmacology; D007376:Interleukin-2 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D018655:Lymphocyte Count; D008297:Male; D012890:Sleep / Q000502:physiology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D016207:Cytokines; D007376:Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D007371:Interferon-gamma; D013006:Growth Hormone; D006854:Hydrocortisone