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.
Chapter: Aging, Sleep, and Immunity[Show abstract] [Hide abstract]
ABSTRACT: It is a truism that sleep remains an important enigma in neurobiology and physiology. It is trite to acknowledge that sleep clearly has an important adaptive value to the organism as a whole, yet defining that function remains elusive (Krueger, Majde, and Obal 2003; Siegel 2003). One prominent thought has been that sleep promotes recovery from infectious challenge. Consistent with this notion are the common observations of lethargy and increased desire to sleep that accompany mild infections such as colds or “the flu.” Accompanying these ideas are those suggesting that the lack of sleep increases susceptibility to infectious disease (Opp and Toth 2003). Despite these widespread beliefs there is little empirical evidence to support the hypotheses that increased sleep aids recovery from, and lack of sleep increases susceptibility to, infections. However, there are data now available addressing the possible molecular regulation of the interactions between infection and altered sleep behavior. Amongst the changes observed are evidence for a cytokine cascade within the brain, including interleukin (IL)-1 and tumor necrosis factor (TNF)-α, along with a number of other substances including growth hormonereleasing hormone (GHRH), prolactin (PL), nitric oxide (NO) and nuclear factor kappa B (NF-kB). These substances, as we shall see below, are also implicated in the regulation of normal spontaneous sleep. The review that follows will focus on altered cytokine production as being of primary importance in sleep physiology in health and disease, but will also pay attention to the role of disruptions in these processes during normal human aging, and its effect on human health.12/2006: pages 133-153;
- Journal of Chronotherapy and Drug Delivery. 12/2010; 1(1):19-25.
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ABSTRACT: The sleep-wake cycle is characterized by complex interactions among the central nervous, the endocrine and the immune systems. Continuous 24-h wakefulness prevents sleep-associated hormone regulation resulting in impaired pro-inflammatory cytokine production. Importantly, cytokines and hormones also modulate the complement system, which in turn regulates several adaptive immune responses. However, it is unknown whether sleep affects the activation and the immunoregulatory properties of the complement system. Here, we determined whether the 24-h sleep-wake cycle has an impact on: (i) the levels of circulating complement factors; and (ii) TLR4-mediated IL-12 production from human IFN-γ primed monocytes in the presence or absence of C5a receptor signaling. For this purpose, we analyzed the blood and blood-derived monocytes of 13 healthy donors during a regular sleep-wake cycle in comparison to 24 h of continuous wakefulness. We found decreased plasma levels of C3 and C4 during nighttime hours that were not affected by sleep. In contrast, sleep was associated with increased complement activation as reflected by elevated C3a plasma levels during nighttime sleep. Sleep deprivation prevented such activation. At the cellular level, C5a negatively regulated TLR4-mediated IL-12p40 and p70 production from human monocytes. Importantly, this regulatory effect of C5a on IL-12p70 production was effective only during daytime hours. Thus, similar to hormones, some complement factors and immunoregulatory properties of C5a are influenced by sleep and the circadian rhythm. Our findings that continuous wakefulness has a negative impact on complement activation may provide a rationale for the immunosupportive functions of sleep.Brain Behavior and Immunity 04/2011; 25(7):1416-26. · 5.61 Impact Factor