Acute sleep fragmentation induces tissue-specific changes in cytokine gene expression and increases serum corticosterone concentration.

Sleep deprivation induces acute inflammation and increased glucocorticosteroids in vertebrates, but effects from fragmented, or intermittent, sleep are poorly understood. Considering the latter is more representative of sleep apnea in humans, we investigated changes in proinflammatory (IL-1β, TNF-α) and anti-inflammatory (TGF-β1) cytokine gene expression in the periphery (liver, spleen, fat, and heart) and brain (hypothalamus, prefrontal cortex, and hippocampus) of a murine model exposed to varying intensities of sleep fragmentation (SF). Additionally, serum corticosterone was assessed. Sleep was disrupted in male C57BL/6J mice using an automated sleep fragmentation chamber that moves a sweeping bar at specified intervals (Lafayette Industries). Mice were exposed to bar sweeps every 20 s (high sleep fragmentation, HSF), 120 s (low sleep fragmentation, LSF), or the bar remained stationary (control). Trunk blood and tissue samples were collected after 24 h of SF. We predicted that HSF mice would exhibit increased proinflammatory expression, decreased anti-inflammatory expression, and elevated stress hormones in relation to LSF and controls. SF significantly elevated IL-1β gene expression in adipose tissue, heart (HSF only), and hypothalamus (LSF only) relative to controls. SF did not increase TNF-α expression in any of the tissues measured. HSF increased TGF-β1 expression in the hypothalamus and hippocampus relative to other groups. Serum corticosterone concentration was significantly different among groups, with HSF mice exhibiting the highest, LSF intermediate, and controls with the lowest concentration. This indicates that 24 h of SF is a potent inducer of inflammation and stress hormones in the periphery, but leads to upregulation of anti-inflammatory cytokines in the brain.