Sleep loss activates cellular inflammation and signal transducer and activator of transcription (STAT) family proteins in humans

Brain Behav Immun. 2015 Jul:47:86-92. doi: 10.1016/j.bbi.2014.09.017. Epub 2014 Oct 17.

Abstract

Sleep disturbance and short sleep duration are associated with inflammation and related disorders including cardiovascular disease, arthritis, diabetes mellitus, and certain cancers. This study was undertaken to test the effects of experimental sleep loss on spontaneous cellular inflammation and activation of signal transducer and activator of transcription (STAT) family proteins, which together promote an inflammatory microenvironment. In 24 healthy adults (16 females; 8 males), spontaneous production of IL-6 and TNF-α in monocytes and spontaneous intranuclear expression of activated STAT1, STAT3, and STAT5 in peripheral blood mononuclear cells (PBMC), monocyte-, and lymphocyte populations were measured in the morning after uninterrupted baseline sleep, partial sleep deprivation (PSD, sleep period from 3a.m. to 7a.m.), and recovery sleep. Relative to baseline, spontaneous monocytic expression of IL-6 and TNF-α was significantly greater after PSD (P<0.02) and after recovery sleep (P<0.01). Relative to baseline, spontaneous monocytic expression of activated STAT1 and STAT5 was significantly greater after recovery sleep (P<0.007 and P<0.02, respectively) but not STAT3 (P=0.09). No changes in STAT1, STAT3, or STAT5 were found in lymphocyte populations. Sleep loss induces activation of spontaneous cellular innate immunity and of STAT family proteins, which together map the dynamics of sleep loss on the molecular signaling pathways that regulate inflammatory and other immune responses. Treatments that target short sleep duration have the potential to constrain inflammation and reduce the risk for inflammatory disorders and some cancers in humans.

Keywords: Flow cytometry; Humans; Immunology; Inflammation; Interleukin-6; Monocytes; Signal transducer and activator of transcription; Sleep; Sleep deprivation; Tumor necrosis factor-α.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Female
  • Humans
  • Inflammation / immunology
  • Inflammation / metabolism
  • Interleukin-6 / metabolism*
  • Leukocytes, Mononuclear / metabolism
  • Male
  • Middle Aged
  • Monocytes / metabolism
  • STAT1 Transcription Factor / metabolism*
  • STAT3 Transcription Factor / metabolism*
  • STAT5 Transcription Factor / metabolism*
  • Sleep Deprivation / immunology*
  • Sleep Deprivation / metabolism
  • Tumor Necrosis Factor-alpha / metabolism*

Substances

  • Interleukin-6
  • STAT1 Transcription Factor
  • STAT1 protein, human
  • STAT3 Transcription Factor
  • STAT5 Transcription Factor
  • Tumor Necrosis Factor-alpha