title: Effects of an interleukin-1 receptor antagonist on human sleep, sleep-associated memory consolidation, and blood monocytes.
abstract: Pro-inflammatory cytokines like interleukin-1 beta (IL-1) are major players in the interaction between the immune system and the central nervous system. Various animal studies report a sleep-promoting effect of IL-1 leading to enhanced slow wave sleep (SWS). Moreover, this cytokine was shown to affect hippocampus-dependent memory. However, the role of IL-1 in human sleep and memory is not yet understood. We administered the synthetic IL-1 receptor antagonist anakinra (IL-1ra) in healthy humans (100mg, subcutaneously, before sleep; n=16) to investigate the role of IL-1 signaling in sleep regulation and sleep-dependent declarative memory consolidation. Inasmuch monocytes have been considered a model for central nervous microglia, we monitored cytokine production in classical and non-classical blood monocytes to gain clues about how central nervous effects of IL-1ra are conveyed. Contrary to our expectation, IL-1ra increased EEG slow wave activity during SWS and non-rapid eye movement (NonREM) sleep, indicating a deepening of sleep, while sleep-associated memory consolidation remained unchanged. Moreover, IL-1ra slightly increased prolactin and reduced cortisol levels during sleep. Production of IL-1 by classical monocytes was diminished after IL-1ra. The discrepancy to findings in animal studies might reflect species differences and underlines the importance of studying cytokine effects in humans.
authors.affiliation: Department of Medical Psychology and Behavioral Neurobiology, University of Tübingen, 72076 Tübingen, Germany.
authors.forename: Eva-Maria
authors.initials: EM
authors.lastname: Schmidt
authors.affiliation: Department of Neuroendocrinology, University of Lübeck, 23538 Lübeck, Germany.
authors.forename: Barbara
authors.initials: B
authors.lastname: Linz
authors.affiliation: Department of Medical Psychology and Behavioral Neurobiology, University of Tübingen, 72076 Tübingen, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Diekelmann
authors.affiliation: Department of Medical Psychology and Behavioral Neurobiology, University of Tübingen, 72076 Tübingen, Germany.
authors.forename: Luciana
authors.initials: L
authors.lastname: Besedovsky
authors.affiliation: Department of Neuroendocrinology, University of Lübeck, 23538 Lübeck, Germany.
authors.forename: Tanja
authors.initials: T
authors.lastname: Lange
authors.affiliation: Department of Medical Psychology and Behavioral Neurobiology, University of Tübingen, 72076 Tübingen, Germany; Center for Integrative Neuroscience (CIN), University of Tübingen, 72076 Tübingen, Germany; German Center for Diabetes Research (DZD) and Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Centre Munich at the University of Tübingen (IDM), 72076 Tübingen, Germany. Electronic address: jan.born@uni-tuebingen.de.
authors.forename: Jan
authors.initials: J
authors.lastname: Born
mesh_terms: D000293:Adolescent; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D019382:Human Growth Hormone / Q000097:blood; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D053590:Interleukin 1 Receptor Antagonist Protein / Q000494:pharmacology*; D008297:Male; D000069077:Memory Consolidation / Q000187:drug effects* / Q000502:physiology; D009000:Monocytes / Q000187:drug effects*; D011388:Prolactin / Q000097:blood; D012890:Sleep / Q000187:drug effects* / Q000502:physiology; D055815:Young Adult
chemical_list: D053590:Interleukin 1 Receptor Antagonist Protein; D019382:Human Growth Hormone; D000324:Adrenocorticotropic Hormone; D011388:Prolactin; D006854:Hydrocortisone
keywords: IL-1ra; Memory consolidation; Monocytes; Prolactin; Sleep