Humoral Links between Sleep and the Immune System

  title={Humoral Links between Sleep and the Immune System},
  author={James Krueger and J A Majde},
  journal={Annals of the New York Academy of Sciences},
Abstract: In the last twenty years we have realized that the immune system synthesizes a class of peptides, termed cytokines, that play a central role in alerting the brain to ongoing inflammation in peripheral tissues. Among the brain's responses to proinflammatory cytokines, or agents that induce these cytokines, are certain alterations in sleep profiles. Characteristically there is an increase in non‐rapid eye movement sleep (NREMS), and NREMS intensity is often accompanied by a decrease in… 
[Sleep and immune system].
Sleep emerges as an important regulator of the immune system since, during sleep, the necessary functions to maintain its balance are carried out, and decreased sleep has deleterious effects that alter the metabolism and produce an increase in the secretion of C-reactive protein, interleukin (IL)-6 and tumor necrosis factor (TNF).
Cytokines and normal sleep
There is increasing evidence of a role for cytokines in regulating spontaneous non-rapid eye movement sleep and there is a significant overlap between neurohormonal systems such as the somatotropic and hypothalamic-pituitary-adrenal axes and cytokines, particularly with regard to their effects on sleep-wake regulation.
Sleep–Immune System Interaction: Advantages and Challenges of Human Sleep Loss Model
Human sleep loss models have been of great help in mechanistic characterization of cytokines in sleep and neuroendocrine components in non-REM sleep, respectively and the paradigm has helped establish sleep's functional characterization because of practical simplicity and often non-ambiguous results.
Humoral sleep regulation; interleukin-1 and tumor necrosis factor.
The influence of cytokines on wakefulness regulation: clinical relevance, mechanisms and methodological problems.
Clinical relevance of this issue arises from the frequency of accidents, injuries and impairment in social functioning due to sleepiness, the occurrence of fatigue syndromes associated with inflammatory diseases, cancer or obesity, the role of wakefulness regulation for the pathophysiology of affective and sleep disorders and sedation as a side effect of psychopharmacological therapy.
Effects of Macrophage Depletion on Sleep in Mice
Cold-induced increase in wakefulness and decrease in NREMS, rapid-eye movement sleep and body temperature were significantly enhanced in macrophage-depleted mice indicating increased cold sensitivity, further evidence for the reciprocal interaction among the immune system, sleep and metabolism.
Role of interleukin‐6 in stress, sleep, and fatigue
Evidence is summarized showing how IL‐6 elevations in the context of inflammatory disease affect the organism, with a focus on sleep‐related symptoms and fatigue; and conversely, how alterations in sleep duration and quality stimulate increased concentrations of IL‐ 6 in the circulation.
The Sleep-Immune Crosstalk in Health and Disease
The induction of a hormonal constellation that supports immune functions is one likely mechanism underlying the immune-supporting effects of sleep, and sleep appears to promote inflammatory homeostasis through effects on several inflammatory mediators, such as cytokines.
Bidirectional Communication between the Brain and the Immune System: Implications for Physiological Sleep and Disorders with Disrupted Sleep
Current understanding of neuroimmune interactions in normal sleep and sleep deprivation, and the influence of these interactions on selected disorders characterized by pathological sleep are reviewed.


Sleep: A Physiologic Role for IL‐1β and TNF‐α a
There is a diurnal rhythm of TNF‐α mRNA and IL‐1β mRNA in brain with highest levels occurring during peak sleep periods, and Mice lacking either the TNF 55‐kD receptor or theIL‐1 type I receptor sleep less than do strain controls.
IL-1 is a mediator of increases in slow-wave sleep induced by CRH receptor blockade.
  • F. Chang, M. Opp
  • Biology, Psychology
    American journal of physiology. Regulatory, integrative and comparative physiology
  • 2000
Data indicate that IL-1 is a mediator of astressin-induced alterations in sleep-wake behavior, and the increase in SWS and the reduction in waking that occur afterAstressin are abolished when animals are pretreated with anti-IL-1beta.
Biochemical regulation of non-rapid-eye-movement sleep.
There is a third group of substances whose significance in sleep regulation is less clear but for which there are two or more lines of evidence suggesting that they may have a role in modulating non-REM sleep (NREMS).
Interleukin-18 promotes sleep in rabbits and rats.
An anti-human IL-18 antibody had little effect on spontaneous sleep in rabbits, although the anti-IL-18 antibodies significantly attenuated muramyl dipeptide-induced sleep, suggesting that IL- 18 is involved in mechanisms of sleep responses to infection.
Rat Strains that Differ in Corticotropin-Releasing Hormone Production Exhibit Different Sleep-Wake Responses to Interleukin 1
The hypothesis that CRH is both a modulator of responses to IL-1 and is involved in the regulation of waking is supported.
CRF/NPY interactions: A potential role in sleep dysregulation in depression and anxiety
Neuropeptide Y (NPY) has neuromodulatory actions on multiple brain functions including endocrine, behavioral, and circadian processes and has been implicated in the pathophysiology of both anxiety
Microbial products and cytokines in sleep and fever regulation.
Cytokines are likely key mediators of fever and sleep responses to infection, and may be beneficial to host defense although this area is relatively uninvestigated.
The Mechanism of Action of Cytokines to Control the Release of Hypothalamic and Pituitary Hormones in Infection
No plays a key role in inducing the changes in release of hypothalamic peptides induced in infection by cytokines, at least in part via induction of inducible NOS.
Modulation by Cytokines of Glucocorticoid Action
It is found that IL‐2 and IL‐6 up‐regulate remarkably the number of GR binding sites and the expression of GR mRNA in peripheral blood mononuclear cells and in osteoblast‐like Saos‐2 cells.