Obstructive sleep apnea is increasing worldwide, leading to disordered sleep patterns and inflammatory responses in brain and peripheral tissues that predispose individuals to chronic disease. Pro-inflammatory cytokines activate the inflammatory response and are normally regulated by glucocorticoids secreted from adrenal glands. However, the temporal dynamics of inflammatory responses and hypothalamic-pituitary-adrenal (HPA) axis activation in relation to acute sleep fragmentation (ASF) are undescribed. Male C57BL/6J mice were exposed to ASF or control conditions (no ASF) over specified intervals (1, 2, 6, and 24 h) and cytokine gene expression (IL-1beta, TNF-alpha) in brain and peripheral tissues as well as serum glucocorticoid and interleukin-6 (IL-6) concentration were assessed. The HPA axis was rapidly activated, leading to elevated serum corticosterone from 1-24 h of ASF compared with controls. This activation was followed by elevated serum IL-6 concentration from 6-24 h of ASF. The tissue to first exhibit increased pro-inflammatory gene expression from ASF was heart (1 h of ASF). In contrast, pro-inflammatory gene expression was suppressed in hypothalamus after 1 h of ASF, but elevated after 6 h. Because the HPA axis was activated throughout ASF, this suggests that brain, but not peripheral, pro-inflammatory responses were rapidly inhibited by glucocorticoid immunosuppression.
Keywords: Cytokines; Glucocorticoids; Inflammation; Interleukin- 6; Interleukin-1; Sleep Fragmentation; Tumor Necrosis Factor.