Disrupted sleep from obstructive sleep apnea or insomnia promotes an inflammatory environment. Studies in mice have shown that experimental sleep fragmentation (SF) increases pro-inflammatory cytokine gene expression in brain and peripheral tissues as well as increasing circulating glucocorticoids. Although glucocorticoids classically exert anti-inflammatory effects at pharmacological concentrations, they may also modulate immune function in a context- and dose-dependent manner. To investigate whether glucocorticoids regulate pro-inflammatory responses, we used a classic adrenalectomy (ADX) ablation and corticosterone (CORT) replacement design. Adult male C57BL/6J mice received bilateral ADX, sham surgery, or ADX with corticosterone (CORT) replacement in drinking water, and were exposed to acute (24h) SF or no SF (NSF). Pro-inflammatory gene expression (IL-1β, TNF-α) was quantified in hippocampus, hypothalamus, and pre-frontal cortex, as well as peripheral tissues including liver, spleen, heart, epididymal white adipose tissue (EWAT). ADX effectively reduced serum corticosterone, while CORT replacement produced pharmacological hormone levels. Pharmacological CORT treatment robustly suppressed pro-inflammatory gene expression across multiple brain regions (prefrontal cortex, hypothalamus) and peripheral tissues (liver, heart, spleen) compared with ADX and/or sham mice, indicating a strong anti-inflammatory effect at elevated glucocorticoid concentrations. In contrast, ADX mice showed modest, tissue-specific increases in inflammatory gene expression, primarily in liver and heart, suggesting limited regulation by physiological corticosterone levels. Sleep fragmentation did not significantly increase pro-inflammatory gene expression compared with controls. In conclusion, corticosterone exerts potent, dose-dependent, and tissue-specific suppression of pro-inflammatory gene expression that is not modulated by acute sleep fragmentation in male mice.
Hm et al. (Wed,) studied this question.