In spite of the fact that some refer to rest as conventional wisdom with no basis in fact where recovery from disease processes is concerned, this is incorrect. There is considerable evidence of a strong relationship between immune responses and sleep (e.g. a form of rest). Here are a few more recent abstracts from The (U.S.) National Library of Medicine's database on this subject:
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Int Rev Neurobiol. 2002;52:93-131.
Brain-immune interactions in sleep.
Marshall L, Born J.
Department of Clinical Neuroendocrinology, Medical University of Lubeck, 23538 Lubeck, Germany.
This chapter discusses various levels of interactions between the brain and the immune system in sleep. Sleep-wake behavior and the architecture of sleep are influenced by microbial products and cytokines. On the other hand, sleep processes, and perhaps also specific sleep states, appear to promote the production and/or release of certain cytokines. The effects of immune factors such as endotoxin and cytokines on sleep reveal species specificity and usually strong dependence on parameters such as substance concentration, time relative to administration or infection with microbial products, and phase relation to sleep and/or the light-dark cycle. For instance, endotoxin increased SWS and EEG SWA in humans only at very low concentrations, whereas higher concentrations increased sleep stage 2 only, but not SWS. In animals, increases in NREM sleep and SWA were more consistent over a wide range of endotoxin doses. Also, administration of pro-inflammatory cytokines such as IL-6 and IFN-alpha in humans acutely disturbed sleep while in rats such cytokines enhanced SWS and sleep. Overall, the findings in humans indicate that strong nonspecific immune responses are acutely linked to an arousing effect. Although subjects feel subjectively tired, their sleep flattens. However, some observations indicate a delayed enhancing effect on sleep which could be related to the induction of secondary, perhaps T-cell-related factors. This would also fit with results in animals in which the T-cell-derived cytokine IL-2 enhanced sleep while cytokines with immunosuppressive functions like IL-4 and L-10 suppressed sleep. The most straightforward similarity in the cascade of events inducing sleep in both animals and humans is the enhancing effect of GHRH on SWS, and possibly the involvement of the pro-inflammatory cytokine systems of IL-1 beta and TNF-alpha. The precise mechanisms through which administered cytokines influence the central nervous system sleep processes are still unclear, although extensive research has identified the involvement of various molecular intermediates, neuropeptides, and neurotransmitters (cp. Fig. 5, Section III.B). Cytokines are not only released and found in peripheral blood mononuclear cells, but also in peripheral nerves and the brain (e.g., Hansen and Krueger, 1997; Marz et al., 1998). Cytokines are thereby able to influence the central nervous system sleep processes through different routes. In addition, neuronal and glial sources have been reported for various cytokines as well as for their soluble receptors (e.g., Kubota et al., 2001a). Links between the immune and endocrine systems represent a further important route through which cytokines influence sleep and, vice versa, sleep-associated processes, including variations in neurotransmitter and neuronal activity may influence cytokine levels. The ability of sleep to enhance the release and/or production of certain cytokines was also discussed. Most consistent results were found for IL-2, which may indicate a sleep-associated increase in activity of the specific immune system. Furthermore, in humans the primary response to antigens following viral challenge is enhanced by sleep. In animals results are less consistent and have focused on the secondary response. The sleep-associated modulation in cytokine levels may be mediated by endocrine parameters. Patterns of endocrine activity during sleep are probably essential for the enhancement of IL-2 and T-cell diurnal functions seen in humans: Whereas prolactin and GH release stimulate Th1-derived cytokines such as IL-2, cortisol which is decreased during the beginning of nocturnal sleep inhibits Th1-derived cytokines. The immunological function of neurotrophins, in particular NGF and BDNF, has received great interest. Effects of sleep and sleep deprivation on this cytokine family are particularly relevant in view of the effects these endogenous neurotrophins can have not only on specific immune functions and the development of immunological memories, but also on synaptic reorganization and neuronal memory formation.
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Ann N Y Acad Sci. 2003 May;992:9-20. R
Humoral links between sleep and the immune system: research issues.
Krueger JM, Majde JA.
Department of Veterinary and Comparative Anatomy, Pharmacology and Physiology, Washington State University, Pullman, Washington 99164-6520, USA.
Krueger@vetmed.wsu.edu
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 rapid eye movement sleep (REMS). Cytokines appear to play a role in normal sleep regulation; during pathology, higher levels of cytokines amplify the physiological cytokine sleep mechanisms. In this review we summarize the extensive literature on the roles of interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-alpha) in sleep regulation, and their interactions with the neuropeptides growth hormone-releasing hormone (GHRH) and corticotropin-releasing hormone (CRH). We reach the tentative conclusion that the sleep-promoting actions of IL-1 and GHRH are mediated via anterior hypothalamic neurons that are receptive to these substances. It also seems likely that TNF-alpha and CRH also influence these neurons. In addition, we discuss an array of research issues raised by these studies that remain to be resolved.
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Nocturnal catecholamines and immune function in insomniacs, depressed patients, and control subjects.
Irwin M, Clark C, Kennedy B, Christian Gillin J, Ziegler M.
Cousins Center for Psychoneuroimmunonology, UCLA Neuropsychiatric Institute, University of California, Los Angeles, CA 90095-7057, USA.
mirwin@ucla.edu
Insomnia predicts cardiovascular and non-cardiovascular disease mortality. This study evaluated EEG sleep, nocturnal sympathetic activity, and daytime measures of immune function in subjects with primary insomnia (n = 17) and patients with current major depression (n = 14) as compared to controls (n = 31). Insomniacs showed disordered sleep continuity along with nocturnal increases of average levels of circulating norepinephrine and decreases of natural killer cell responses, whereas depressed patients showed declines of natural killer cell activity, but no differences of EEG sleep or nocturnal catecholamines as compared to controls. Impairments of sleep efficiency correlated with nocturnal elevations of norepinephrine in the insomniacs but not in the depressives or controls. These data indicate that insomnia is associated with nocturnal sympathetic arousal and declines of natural immunity, and further support the role of sleep in the regulation of sympathetic nervous and immune system functioning.
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Neural-immune interactions in the regulation of sleep.
Opp MR, Toth LA.
Department of Anesthesiology, University of Michigan School of Medicine, Ann Arbor 48109-0615, USA.
mopp@med.umich.edu
Interactions between sleep and the immune system have been recognized for millennia. The lethargy and increased desire to sleep that accompany mild infections such as colds or "the flu" are common experiences. These experiences have fostered the belief that sleep promotes recovery from infectious challenge. Another common belief is that the lack of sleep increases susceptibility to infectious disease. However, despite these age-old and widespread beliefs, surprisingly little empirical evidence supports the hypotheses that increased sleep aids recovery from, and lack of sleep increases susceptibility to, infections. Although research conducted over the last 30 years has clearly demonstrated that sleep is altered during the course of infection, few experiments have directly tested the functional impact of sleep on responses to immune challenge. We will review relevant literature documenting that sleep patterns do indeed change during states of infectious disease, discuss potential mediators of these alterations in behavior, and finally address the issue of whether sleep or sleep loss impacts the ability of the host to mount an appropriate immune response.
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