Abstract
Interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) are involved in physiologic sleep regulation. Administration of exogenous IL-1 beta or TNF-alpha induces increased non-rapid eye movement sleep (NREMS). Inhibition of IL-1 or TNF reduces spontaneous sleep. There is a diurnal rhythm of TNF-alpha mRNA and IL-1 beta mRNA in brain with highest levels occurring during peak sleep periods. Mice lacking either the TNF 55-kD receptor or the IL-1 type I receptor sleep less than do strain controls. IL-1 beta and TNF-alpha are part of a larger biochemical cascade involved in sleep regulation; other somnogenic substances in this cascade include growth hormone-releasing hormone and nitric oxide. Several additional substances are involved in inhibitory feedback mechanisms, some of which inhibit IL-1 and TNF. A major challenge to sleep research is to define how and where these molecular steps produce sleep.
Publication types
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Research Support, U.S. Gov't, P.H.S.
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Review
MeSH terms
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Animals
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Antigens, CD / metabolism
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Antigens, CD / physiology
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Brain / immunology
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Brain / physiology*
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Circadian Rhythm
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Cytokines / physiology*
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Fever / physiopathology
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Gene Expression Regulation
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Humans
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Interleukin-1 / genetics
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Interleukin-1 / physiology*
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Mice
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Mice, Knockout
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Models, Biological
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Receptors, Interleukin-1 / deficiency
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Receptors, Interleukin-1 / physiology
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Receptors, Tumor Necrosis Factor / deficiency
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Receptors, Tumor Necrosis Factor / metabolism
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Receptors, Tumor Necrosis Factor / physiology
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Receptors, Tumor Necrosis Factor, Type I
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Sleep / immunology
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Sleep / physiology*
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Transcription, Genetic
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Tumor Necrosis Factor-alpha / genetics
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Tumor Necrosis Factor-alpha / physiology*
Substances
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Antigens, CD
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Cytokines
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Interleukin-1
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Receptors, Interleukin-1
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Receptors, Tumor Necrosis Factor
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Receptors, Tumor Necrosis Factor, Type I
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Tumor Necrosis Factor-alpha