Differential acute effects of sleep on spontaneous and stimulated production of tumor necrosis factor in men
Abstract
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.
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Monocytes show a marked increase at night in their response to TLR-4 stimulation by LPS.
“there is evidence of a striking night-time increase in the ability of monocytes to respond to challenge (ie, TLR-4 activation with LPS) (Dimitrov et al, 2015)”
From Sleep health: Reciprocal regulation of sleep and innate immunity (2017) · cites this paper as Dimitrov et al, 2015
Intracellular IL-6 production is not altered acutely during sleep compared with nocturnal wakefulness, but is increased in the morning after one night of partial sleep loss in healthy humans.
“Intracellular IL-6 production was not altered acutely during sleep compared with nocturnal wakefulness (147), but was increased in the morning after one night of partial sleep loss in healthy humans (89, 256, 262, 264).”
From The Sleep-Immune Crosstalk in Health and Disease (2019) · cites this paper as [147]
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A crosstalk between the immune system and obstructive sleep apnea
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- Authors
- Dimitrov, S., Besedovsky, L., Born, J., & Lange, T.
- Affiliations
- University of Tübingen (DE)
- University of Lübeck (DE)
- Corresponding author
- Dimitrov, Stoyan
- Venue
- Brain, Behavior, and Immunity
- Publisher
- Elsevier BV
- Published
- 2015-07
- Volume
- 47
- Pages
- 201-210
- ISSN
- 0889-1591 (ISSN-L)
- OpenAlex
- W1990266974
- Cited by
- 56
- References
- 115
- Citations by year
- 2026: 2 · 2025: 6 · 2024: 9 · 2023: 8 · 2022: 7 · 2021: 2 · 2020: 6 · 2019: 5 · 2018: 2 · 2017: 2 · 2016: 4 · 2015: 3
- FWCI
- 1.67
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Brain Behavior and Immunity (publishedVersion)
- PubMed (publishedVersion)
- Site cant be reached (submittedVersion)
- Funders
- Deutsche Forschungsgemeinschaft (TR-SFB 654)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and Work-Related Fatigue
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Keywords
- sleep, TNF-α, lipopolysaccharide stimulation, monocytes, immune response, sleep-wake cycle, cortisol, norepinephrine, prolactin, sleep deprivation
- MeSH terms
- Adolescent, Adult, Circadian Rhythm, Humans, Lipopolysaccharides, Male, Monocytes, Sleep, Tumor Necrosis Factor-alpha, Wakefulness, Young Adult
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