Sleep Deprivation and Activation of Morning Levels of Cellular and Genomic Markers of Inflammation

TLDR

Inflammation is linked to cardiovascular disease, arthritis, diabetes, and mortality, yet the impact of sleep loss on cellular and genomic mechanisms driving cytokine activity remains unknown. The study aimed to assess how partial sleep deprivation alters monocyte cytokine gene transcription and to identify transcription‑control pathways that may mediate these effects, with the goal of informing sleep‑based interventions to reduce inflammation. The authors recruited 30 healthy adults, measured monocyte intracellular cytokine production across three baseline days and after a 4‑hour sleep loss, and performed DNA microarray analyses to examine cytokine gene transcription and related regulatory pathways. Partial sleep deprivation markedly increased monocyte IL‑6 and TNF‑α production and their mRNA levels, activated NF.

Abstract

Inflammation is associated with increased risk of cardiovascular disorders, arthritis, diabetes mellitus, and mortality. The effects of sleep loss on the cellular and genomic mechanisms that contribute to inflammatory cytokine activity are not known.In 30 healthy adults, monocyte intracellular proinflammatory cytokine production was repeatedly assessed during the day across 3 baseline periods and after partial sleep deprivation (awake from 11 pm to 3 am). We analyzed the impact of sleep loss on transcription of proinflammatory cytokine genes and used DNA microarray analyses to characterize candidate transcription-control pathways that might mediate the effects of sleep loss on leukocyte gene expression.In the morning after a night of sleep loss, monocyte production of interleukin 6 and tumor necrosis factor alpha was significantly greater compared with morning levels following uninterrupted sleep. In addition, sleep loss induced a more than 3-fold increase in transcription of interleukin 6 messenger RNA and a 2-fold increase in tumor necrosis factor alpha messenger RNA. Bioinformatics analyses suggested that the inflammatory response was mediated by the nuclear factor kappaB inflammatory signaling system as well as through classic hormone and growth factor response pathways.Sleep loss induces a functional alteration of the monocyte proinflammatory cytokine response. A modest amount of sleep loss also alters molecular processes that drive cellular immune activation and induce inflammatory cytokines; mapping the dynamics of sleep loss on molecular signaling pathways has implications for understanding the role of sleep in altering immune cell physiologic characteristics. Interventions that target sleep might constitute new strategies to constrain inflammation with effects on inflammatory disease risk.