Sleep depth and fatigue: Role of cellular inflammatory activation

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.

Research highlights
► 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.
► We report that evening stimulated monocyte production of interleukin-6 (IL-6), but not tumor necrosis factor a (TNF- a), was negatively associated with slow wave sleep in a sample of healthy adults.
► Moreover, evening stimulated production of IL-6 was associated with fatigue the following day.
► In contrast, stimulated monocyte production of IL-6 was positively associated with rapid-eye movement (REM) sleep duration during the first sleep cycle.
► These results indicate that increases in stimulated monocyte production of IL6 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.