Obstructive Sleep Apnea and Inflammation: Proof of Concept Based on Two Illustrative Cytokines

Abstract

Obstructive sleep apnea syndrome (OSAS) is a markedly prevalent condition across the lifespan, particularly in overweight and obese individuals, which has been associated with an independent risk for neurocognitive, behavioral, and mood problems as well as cardiovascular and metabolic morbidities, ultimately fostering increases in overall mortality rates. In adult patients, excessive daytime sleepiness (EDS) is the most frequent symptom leading to clinical referral for evaluation and treatment, but classic EDS features are less likely to be reported in children, particularly among those with normal body-mass index. The cumulative evidence collected over the last two decades supports a conceptual framework, whereby sleep-disordered breathing in general and more particularly OSAS should be viewed as low-grade chronic inflammatory diseases. Accordingly, it is assumed that a proportion of the morbid phenotypic signature in OSAS is causally explained by underlying inflammatory processes inducing end-organ dysfunction. Here, the published links between OSAS and systemic inflammation will be critically reviewed, with special focus on the pro-inflammatory cytokines tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6), since these constitute classical prototypes of the large spectrum of inflammatory molecules that have been explored in OSAS patients.

Inflammatory Factors: Nonobese Pediatric Obstructive Sleep Apnea and Adenotonsillectomy

“…Previous studies have shown that plasma pro-inflammatory cytokines, such as high density-CRP (HS-CRP), TNF-α, IL-1β, IL-6, and IL-10, were elevated in children with OSA. Besides, the expression ratio of IL-10 and TNF-α was not normalized even after adenotonsillectomy [12]. In our previous study, we reported that HS-CRP, IL-17, and IL-23 were elevated in children with OSA compared with healthy controls [11] and that most of them had tonsil or adenoid hypertrophy.…”

“…and Interferon-γ (IFN-γ) are related to pediatric OSA. A recent review article showed that plasma IL-6 level was significantly reduced after adenotonsillectomy (T&A) in patients with pediatric OSA, especially those with obesity [12]. However, the results of previous studies are still ambiguous.…”

Interleukin-6 and vitamin D serum levels in patients with obstructive sleep apnea syndrome before and after long-term continuous positive airway pressure treatment

“…Our ndings support that patients with OSAS have higher pro-in ammatory cytokine basal levels. OSAS in both adults and children has been found to promote a persistently low-intensity in ammatory state, expressed by IL-6 [9]. The concentration of IL-6 has been comprehensively evaluated as a contributor to the regulation of sleep in brain areas such as the hypothalamus and hippocampus [16].…”

“…Importantly, it has been demonstrated that increases in in ammatory markers in OSAS patients likely re ect the presence of underlying silent or overt end-organ morbidity [9]. IL-6 induces oxidative stress and promotes NF-κB-dependent endothelial dysfunction [24,38].…”

“…Although there are contradictory data [8], most studies support that IL-6 serves as a reliable reporter or an actual effector of either OSAS or OSAS-associated morbidities [9]. Furthermore, it has been reported that continuous positive airway pressure (CPAP) therapy decreases IL-6 levels in OSAS patients [10].…”