title: Systemic immune parameters and sleep after ultra-low dose administration of IL-2 in healthy men.
abstract: A somnogenic function is suspected for various cytokines. Foregoing experiments in humans indicated a selective increase in the production of interleukin-2 (IL-2) during sleep as compared with nocturnal wakefulness. Here, we examined whether conversely, IL-2 exerts a promoting influence on sleep. Also, the effects of IL-2 administered at ultra-low doses on systemic immune and endocrine parameters were assessed. Eighteen healthy men participated in three night sessions, receiving subcutaneously at 19:00 h either placebo or recombinant human IL-2 at doses of 1000 and 10,000 IU/kg bw. Polysomnographical recordings were obtained between 23:00 and 07:00 h. Blood was collected repeatedly to determine (i) white blood cell (WBC) counts including the enumeration of monocytes, natural killer (NK) cells, and lymphocyte subsets, (ii) serum concentrations of IL-2, soluble IL-2 receptor (sIL-2r), IL-4, IL-6, and interferon-gamma (IFN-gamma), and (iii) concentrations of adrenocorticotropin (ACTH), cortisol, thyreotropin (TSH), and growth hormone (GH). Changes after 1000 IU/kg bw IL-2 generally remained non-significant. However, distinct effects occurred after 10,000 IU/kg bw IL-2, inducing serum IL-2 concentrations selectively activating the high affinity IL-2 receptor. At this dose, IL-2 reduced the number of circulating lymphocytes (including all major subtypes) and NK cells, while counts of monocytes and neutrophils were increased. IL-4 release was stimulated and IFN-gamma concentration reduced after IL-2. Also, IL-2 increased the TSH concentration. There were no hints at a sleep promoting effect of IL-2. Immune changes suggest that nocturnal IL-2 administration induces a shift towards Th2 mediated defense.
authors.affiliation: Department of Internal Medicine, University of Lübeck, Germany.
authors.forename: Tanja
authors.initials: T
authors.lastname: Lange
authors.forename: Lisa
authors.initials: L
authors.lastname: Marshall
authors.forename: Ernst
authors.initials: E
authors.lastname: Späth-Schwalbe
authors.forename: Horst-Lorenz
authors.initials: HL
authors.lastname: Fehm
authors.forename: Jan
authors.initials: J
authors.lastname: Born
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage* / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D018592:Cross-Over Studies; D004311:Double-Blind Method; D006339:Heart Rate / Q000187:drug effects; D019382:Human Growth Hormone / Q000097:blood; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007279:Injections, Subcutaneous; D007371:Interferon-gamma / Q000097:blood; D007376:Interleukin-2 / Q000008:administration & dosage* / Q000097:blood; D015847:Interleukin-4 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D007958:Leukocyte Count; D008297:Male; D015213:Neuroimmunomodulation / Q000187:drug effects; D010976:Platelet Count; D015375:Receptors, Interleukin-2 / Q000097:blood; D012890:Sleep / Q000187:drug effects*; D012995:Solubility
chemical_list: D018712:Analgesics, Non-Narcotic; D007376:Interleukin-2; D015850:Interleukin-6; D015375:Receptors, Interleukin-2; D019382:Human Growth Hormone; D015847:Interleukin-4; D007371:Interferon-gamma; D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone