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.
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ABSTRACT: To review concepts of neuroendocrinoimmunology and provide an overview of the role of immune dysregulation, stress, and the understanding of the pathogenesis and treatment of allergic and autoimmune diseases. Articles include original research papers, review articles, and references identified from the bibliographies of pertinent articles. Neuroendocrine hormones triggered during stress may lead to immune dysregulation or altered or amplified cytokine production, resulting in atopic, autoimmune diseases or decreased host defense. Various types of transmitter substances of the neuroendocrine-immune (NEI) network include epinephrine, norepinephrine, acetylcholine, substance P, vasoactive intestinal peptide, glucagon, insulin, cytokines, growth factors, and numerous other mediators. The stress response and induction of a dysregulation of cytokine balance can trigger the hypothalamic-pituitary-adrenal axis and sympathetic nervous system. Disorders in which abnormalities in immune function are mediated by the NEI network include allergic diseases: allergic rhinitis, atopic dermatitis, and gastro-intestinal allergies and asthma through overproduction of neuropeptides and cytokines. The multiple roles of Th2 cells in maintaining allergic inflammation and altering the balance between Th1 and Th2 responses are important mechanisms for allergic inflammation and tissue damage. In addition, several autoimmune diseases mediated by NEI network such as rheumatoid arthritis, systemic lupus erythematosus, and diabetes mellitus can be attributable to immune dysregulation. Understanding the NEI network will contribute to novel treatments for immediate and late allergic reactions. Chronic stress or depression could lead to decreased host defenses, decreased response to vaccines, viral susceptibility, or malignancy. Treatment of allergic, autoimmune diseases and asthma should include stress management and behavioral intervention to prevent stress-related immune imbalances.Annals of allergy, asthma & immunology: official publication of the American College of Allergy, Asthma, & Immunology 07/2003; 90(6 Suppl 3):34-40. · 3.45 Impact Factor
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ABSTRACT: The molecular mechanisms which govern the biosynthesis and secretion of the various T cell-derived lymphokines are poorly understood at this time, in spite of their tremendous importance to the control of the mammalian immune system. Here we provide compelling evidence that production of the murine T cell growth factors interleukin (IL) 2 and IL4 are differentially regulated by glucocorticoid (GCS) hormones. Under conditions where IL2 production is reduced by GCS hormones, IL4 production is increased. In vivo, this effect on T cell production of growth factors is manifest at low GCS concentrations that are well within physiologic ranges. In vitro, splenocytes isolated from antigen-stimulated donors, as well as antigen-specific cloned T cell lines, undergo alterations in their capacity to secrete T cell growth factors when stimulated with antigens in the presence of GCS. Responses normally dominated by IL2 are dramatically shifted to a condition where IL4 represents the major species of T cell growth factor produced. Similar changes in the pattern of T cell growth factor production are observed following short pulses with low-dose GCS in vitro, and the steroid-induced depression in IL2 production can be reversed and/or inhibited by treatment with the potent steroid antagonist RU486. Our results imply that GCS hormones, presumably through their capacity to activate a specified family of ligand-dependent transcriptional regulatory proteins (steroid hormone receptors), function to control the pattern of lymphokines produced by activated T cells. Steroid-mediated regulation of lymphokine gene expression could serve to dictate the types of immune effector mechanisms which can be initiated subsequent to antigen exposure.European Journal of Immunology 01/1990; 19(12):2319-25. · 4.97 Impact Factor
- Annals of Allergy Asthma & Immunology - ANN ALLERGY ASTHMA IMMUNOL. 01/1998; 80(6):509-516.