Why sleep is important for health: a psychoneuroimmunology perspective

Abstract

Sleep has a critical role in promoting health. Research over the past decade has documented that sleep disturbance has a powerful influence on the risk of infectious disease, the occurrence and progression of several major medical illnesses including cardiovascular disease and cancer, and the incidence of depression. Increasingly, the field has focused on identifying the biological mechanisms underlying these effects. This review highlights the impact of sleep on adaptive and innate immunity, with consideration of the dynamics of sleep disturbance, sleep restriction, and insomnia on (a) antiviral immune responses with consequences for vaccine responses and infectious disease risk and (b) proinflammatory immune responses with implications for cardiovascular disease, cancer, and depression. This review also discusses the neuroendocrine and autonomic neural underpinnings linking sleep disturbance and immunity and the reciprocal links between sleep and inflammatory biology. Finally, interventions are discussed as effective strategies to improve sleep, and potential opportunities are identified to promote sleep health for therapeutic control of chronic infectious, inflammatory, and neuropsychiatric diseases.

Keywords: adaptive immunity; cancer; cardiovascular disease; depression; infectious disease; inflammation; innate immunity; insomnia; psychoneuroimmunology; sleep; sleep deprivation; sleep restriction; vaccine.

Figures

Figure 1

Sleep disturbance and adaptive immunity. The hypothalamus-pituitary-adrenal axis distributes glucocorticoid hormones through the blood to regulate gene expression in virtually every cell of the body. Sleep disturbance results in hormone activation of the glucocorticoid receptor in leukocytes, which leads to a profound suppression antiviral gene programs [e.g., interferon regulatory factor (IRF)-mediated transcription of type I interferons (IFNs) such as the IFNA and IFNB genes]. Sleep disturbance also activates nerve fibers from the sympathetic nervous system (SNS) to release the neurotransmitter norepinephrine into primary and secondary lymphoid organs, all other major organ systems including the vasculature and perivascular tissues as well as many other peripheral tissues. SNS neural fibers can also stimulate the adrenal gland to release stored epinephrine into the systemic circulation. Both neuromediators stimulate leukocyte adrenergic receptors (e.g., ADRB2) to repress IRF-mediated antiviral IFN response gene (IRG) programs. Sleep also induces the release of growth hormone during the early part of the night, and this hormone acts to enhance the proliferation and differentiation of T cells as well as to promote type 1 cytokine activity; when sleep is disrupted, a reduced amount of growth hormone is released. Suppression of IRF-mediated IRG programs leads to a shift in Th1 to Th2 balance, with decreases in Th1 cell production of IFN and increases in Th2 cell production of interleukin-10 (IL-10). This suppression of adaptive immune response is thought to contribute to increased susceptibility to infectious disease and decreased response to vaccines. Abbreviations: ACTH, adrenocorticotropic hormone; EEG, electroencephalogram.

Figure 2

Sleep disturbance and innate immunity. Following a night of sleep loss, or during a period of sleep disturbance, nerve fibers from the sympathetic nervous system (SNS) release the neurotransmitter norepinephrine into primary and secondary lymphoid organs and stimulate the adrenal gland to release stored epinephrine into systemic circulation. Both neuromediators stimulate leukocyte adrenergic receptors (e.g., ADRB2) and activate nuclear factor (NF)-κB-mediated inflammatory programs. Intrinsic circuits detect microbes via pattern recognition receptors (PRRs) such as the Toll-like receptor-4 (TLR4) and stimulate inflammatory gene expression via transcription factors such as NF-κB. The production of proinflammatory cytokines interleukin (IL)-6 and tumor necrosis factor-α (TNFα) occurs. Bidirectional links between the brain and periphery allow the brain to regulate inflammatory activity, and inflammatory activity in turn can influence neural processes in the brain and alter sleep. When this dynamic is induced by sustained sleep disturbance, a feed-forward dysregulation of sleep can occur, which may also confer increased risk for inflammation-related disorders such as cardiovascular disease, cancer, and major depressive disorder.