Bidirectional Communication between the Brain and the Immune System: Implications for Physiological Sleep and Disorders with Disrupted Sleep

Abstract

This review describes mechanisms of immune-to-brain and brain-to-immune signaling involved in mediating physiological sleep and altered sleep with disease. The central nervous system (CNS) modulates immune function by signaling target cells of the immune system through autonomic and neuroendocrine pathways. Neurotransmitters and hormones produced and released by these pathways interact with immune cells to alter immune functions, including cytokine production. Cytokines produced by cells of the immune and nervous systems regulate sleep. Cytokines released by immune cells, particularly interleukin-1β and tumor necrosis factor-α, signal neuroendocrine, autonomic, limbic and cortical areas of the CNS to affect neural activity and modify behaviors (including sleep), hormone release and autonomic function. In this manner, immune cells function as a sense organ, informing the CNS of peripheral events related to infection and injury. Equally important, homeostatic mechanisms, involving all levels of the neuroaxis, are needed, not only to turn off the immune response after a pathogen is cleared or tissue repair is completed, but also to restore and regulate natural diurnal fluctuations in cytokine production and sleep. The immune system’s ability to affect behavior has important implications for understanding normal and pathological sleep. Sleep disorders are commonly associated with chronic inflammatory diseases and chronic age- or stress-related disorders. The best studied are rheumatoid arthritis, fibromyalgia and chronic fatigue syndromes. This article reviews our current understanding of neuroimmune interactions in normal sleep and sleep deprivation, and the influence of these interactions on selected disorders characterized by pathological sleep.

Sleep after Vaccination Boosts Immunological Memory

“…4). SWS, a brain state hallmarked by EEG SWA, stimulates release of immunostimulating hormones like GH and prolactin and inhibits immunosuppressive cortisol (7,8,19). These hormones are not only uniquely regulated by sleep but also affect the interaction between APC and Th cell and the response to vaccination, which is increased by GH and prolactin but reduced by cortisol (22)(23)(24).…”

“…Age and body weight were added as covariates in the analyses of the Th cell and Ab response. The ANOVA model was used also to specify subsequently effects at single time points and for time periods (i.e., for average values over respective periods after the first [weeks 0-8], second [weeks [8][9][10][11][12][13][14][15][16], and third inoculation [weeks [16][17][18][19][20]), for the entire period throughout weeks 0-20, and for the 1-y period (weeks 0-52), when main effects for the sleep/wake factor or sleep/wake 3 time interactions were revealed to be significant. Where appropriate, df were corrected following the Greenhouse-Geisser procedure.…”

“…Immunostimulating hormones like GH and prolactin as well as immunosuppressive hormones such as cortisol and catecholamines are strongly regulated by sleep (7,8,19). We sampled blood during the nights after vaccination (every 1.5 h) to assess a potential impact of these hormones on the HAVspecific Th cell response (Supplemental Fig.…”

“…Compared with wakefulness, sleep on the nights after HBs vaccination significantly enhanced both the CD40L + HBs-specific Th cell response and the Ab response, although overall, these effects appeared to be less consistent than for the HAV vaccination. The enhancing effect of sleep on the frequency of HBs-specific Th cells became significant after the second inoculation (p = 0.05, for weeks [8][9][10][11][12][13][14][15][16] and continued during weeks 16-20 after the third inoculation (p = 0.05) (Supplemental Fig. 3A).…”

“…Sleep impacts APC and Th cell traffic and facilitates the release of endogenous adjuvants like growth hormone (GH), prolactin, and APC-derived IL-12, whereas it lowers the release of immunosuppressive hormones like cortisol (7)(8)(9). In this study, we used an experimental vaccination approach against hepatitis A virus (HAV) to examine whether these effects of sleep can boost immunological memory formation.…”