Sleep: A Physiologic Role for IL-1β and TNF-α

• Published in: Annals of the New York Academy of Sciences Vol. 856; no. 1; pp. 148 - 159
• Main Authors: KRUEGER, JAMES M., FANG, JIDONG, TAISHI, PING, CHEN, ZUTANG, KUSHIKATA, TETSUYA, GARDI, JANOS
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-09-1998
• Subjects: Animals; Antigens, CD - metabolism; Antigens, CD - physiology; Brain - immunology; Brain - physiology; Circadian Rhythm; Cytokines - physiology; Fever - physiopathology; Gene Expression Regulation; Humans; Interleukin-1 - genetics; Interleukin-1 - physiology; Mice; Mice, Knockout; Models, Biological; Receptors, Interleukin-1 - deficiency; Receptors, Interleukin-1 - physiology; Receptors, Tumor Necrosis Factor - deficiency; Receptors, Tumor Necrosis Factor - metabolism; Receptors, Tumor Necrosis Factor - physiology; Receptors, Tumor Necrosis Factor, Type I; Sleep - immunology; Sleep - physiology; Transcription, Genetic; Tumor Necrosis Factor-alpha - genetics; Tumor Necrosis Factor-alpha - physiology
• ISSN: 0077-8923; 1749-6632
• DOI: 10.1111/j.1749-6632.1998.tb08323.x

Interleukin‐1β (IL‐1β) and tumor necrosis factor‐α (TNF‐α) are involved in physiologic sleep regulation. Administration of exogenous IL‐1β or TNF‐α induces increased non‐rapid eye movement sleep (NREMS). Inhibition of IL‐1 or TNF reduces spontaneous sleep. There is a diurnal rhythm of TNF‐α mRNA and IL‐1β 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‐1β and TNF‐α 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.