Sleep depth and fatigue: role of cellular inflammatory activation

Brain Behav Immun. 2011 Jan;25(1):53-8. doi: 10.1016/j.bbi.2010.07.245. Epub 2010 Jul 23.


Individuals with underlying inflammation present with a high prevalence of non-specific co-morbid symptoms including sleep disturbance and fatigue. However, the association between cellular expression of proinflammatory cytokines, alterations of sleep depth and daytime fatigue has not been concurrently examined. In healthy adults (24-61 years old), evening levels of monocyte intracellular proinflammatory cytokine production were assessed prior to evaluation of polysomnographic sleep and measures of fatigue the following day. Stimulated monocyte production of interleukin-6 (IL-6), but not tumor necrosis factor α (TNF-α), was negatively associated with slow wave sleep (ΔR²=.17, p=.029). In contrast, stimulated monocyte production of IL-6 was positively associated with rapid-eye movement (REM) sleep duration during the first sleep cycle (ΔR²=.26, p<.01). Moreover, evening stimulated production of IL-6 was associated with fatigue the following day (ΔR²=.17, p=.05). Mediation analyses showed that slow wave sleep, but not REM sleep duration, mediated the relationship between evening levels of IL-6 production and daytime fatigue. These results indicate that increases in stimulated monocyte production of IL-6 may be associated with decreases in slow wave sleep and increases in REM sleep duration. Relative loss of slow wave sleep may be one pathway through which cellular inflammation leads to daytime fatigue.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cytokines / biosynthesis
  • Cytokines / blood
  • Fatigue / physiopathology*
  • Female
  • Humans
  • Inflammation / physiopathology*
  • Interleukin-6 / biosynthesis
  • Interleukin-6 / blood
  • Male
  • Middle Aged
  • Monocytes / metabolism
  • Polysomnography
  • Sleep / physiology*
  • Sleep Stages / physiology
  • Sleep, REM / physiology
  • Surveys and Questionnaires
  • Tumor Necrosis Factor-alpha / metabolism
  • Young Adult


  • Cytokines
  • Interleukin-6
  • Tumor Necrosis Factor-alpha