Intracerebroventricular injection of TNF-α promotes sleep and is recovered in cervical lymph
Open accessAbstract
Recent studies have shown that the central nervous system (CNS) communicates with the periphery by the drainage of cerebrospinal fluid and brain interstitial fluid into blood and lymph. We hypothesized that tumor necrosis factor (TNF)-α would not only influence the CNS by promoting sleep but also would be directly transmitted into the peripheral immune system. Five hundred nanograms of 125 I-labeled TNF-α were injected into the lateral ventricles of the brain of six sheep and sampled in venous blood and cervical and prescapular lymph every 30 min for 6 h. 125 I-TNF-α was measured in lymph nodes and control fat, skin, and muscle tissues 6 h postinjection.125 I-TNF-α was detected in the cervical lymphatics within the first 30 min and peaked within 2–3 h. 125 I-TNF-α counts were elevated in the nodes of the head and neck region. Polysomnographic recordings of four animals showed that TNF-α induced a significant increase in slow-wave sleep at postinjection hours 4 and 5. CNS TNF-α and its direct drainage into the lymphatic system may influence both the sleeping/waking brain and peripheral immune functions.
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Stimulated TNF production in humans is acutely reduced during sleep compared with nocturnal wakefulness when measured in supernatant or intracellularly in CD8 T cells, but increased when measured in monocytes.
“Stimulated production of TNF in humans has been found to be acutely reduced during sleep compared with nocturnal wakefulness when measured in the supernatant (552) or intracellularly in CD8 T cells (149), but increased when measured in monocytes (146).”
From The Sleep-Immune Crosstalk in Health and Disease (2019) · cites this paper as [146]
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The Sleep-Immune Crosstalk in Health and Disease
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- Authors
- Dickstein, J. B., Moldofsky, H., Lue, F. A., & Hay, J. B.
- Affiliations
- Centre for Sleep and Chronobiology and
- University of Toronto (CA)
- ORCID
- Moldofsky, Harvey
- Venue
- American Journal of Physiology-Regulatory, Integrative and Comparative Physiology
- Publisher
- American Physiological Society
- Published
- 1999-04-01
- Volume
- 276
- Issue
- 4
- Pages
- R1018-R1022
- ISSN
- 0363-6119 (ISSN-L)
- 1522-1490
- OpenAlex
- W1791802991
- Cited by
- 54
- References
- 31
- Citations by year
- 2025: 1 · 2024: 2 · 2023: 1 · 2022: 1 · 2021: 3 · 2020: 2 · 2019: 3 · 2017: 2 · 2013: 1 · 2012: 5
- FWCI
- 2.39
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- American Journal of Physiology-Regulatory, Integrative and Comparative Physiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of Toronto
- National Heart, Lung, and Blood Institute (HL49264, P01HL049264, HL38901, HL39050)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Keywords
- TNF-α, intracerebroventricular administration, sleep, slow-wave sleep, lymphatic drainage, cerebrospinal fluid, peripheral immune system, sheep, polysomnography
- MeSH terms
- Animals, Brain Chemistry, Female, Humans, Injections, Intraventricular, Lymph, Lymph Nodes, Neck, Serum Albumin, Sheep, Sleep, Sleep Stages, Tumor Necrosis Factor-alpha
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