Differential acute effects of sleep on spontaneous and stimulated production of tumor necrosis factor in men

Brain Behav Immun. 2015 Jul;47:201-10. doi: 10.1016/j.bbi.2014.11.017. Epub 2014 Dec 10.


Tumor necrosis factor (TNF) is considered a key molecule in the regulation of sleep in health and disease. Conversely, sleep compared to sleep deprivation can modulate TNF release, but overall results are conflicting. In this study we focused on the influence of sleep on spontaneous, i.e., unstimulated TNF production, which might be involved in sleep regulation under normal non-infectious conditions, and on lipopolysaccharide (LPS)-stimulated TNF production, which reflects the capacity of the immune system to respond to a pathogen. To this end, we monitored 10 healthy men during a regular sleep-wake cycle and during 24h of wakefulness while blood was sampled repeatedly to analyze circulating TNF levels in serum as well as intracellular TNF production in monocytes spontaneously and after stimulation with LPS employing whole blood cell cultures. In addition we assessed numbers of monocyte subsets and levels of various hormones in blood. In comparison with nocturnal wakefulness, sleep acutely decreased serum TNF levels, with no parallel decrease in spontaneous monocytic TNF production, but was associated with a striking nighttime increase in the percentage of TNF producing monocytes after stimulation with LPS. The following day circulating TNF showed a reverse pattern with higher levels after regular sleep than after the nocturnal vigil. The mechanisms mediating the differential effects of sleep on circulating TNF (acutely decreased) vs. stimulated monocytic TNF production (acutely increased) remain unclear, although explorative correlational analyses pointed to a regulatory involvement of cortisol, norepinephrine and prolactin. The acute enhancing effect of sleep on LPS stimulated monocytic TNF production adds to the notion that nocturnal sleep favors immune defense to a microbial challenge.

Keywords: Circadian rhythm; Hormones; Monocytes; Sleep; TNF.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Circadian Rhythm / drug effects
  • Circadian Rhythm / physiology*
  • Humans
  • Lipopolysaccharides / pharmacology
  • Male
  • Monocytes / drug effects
  • Monocytes / metabolism*
  • Sleep / drug effects
  • Sleep / physiology*
  • Tumor Necrosis Factor-alpha / blood*
  • Wakefulness / drug effects
  • Wakefulness / physiology
  • Young Adult


  • Lipopolysaccharides
  • Tumor Necrosis Factor-alpha