Abstract

BackgroundObstructive sleep apnea (OSA) is a risk factor for cardiovascular disease, metabolic disorders, and cognitive dysfunction. Current thinking links chronic intermittent hypoxia (CIH) with oxidative stress and systemic inflammation. However, the sequence of events leading to the morbidities associated with OSA is poorly understood in children. Monocytes are known to be altered by chronic hypoxia. Thus in this prospective study, we investigated inflammatory cytokine profiles from cultures of peripheral blood mononuclear cells (PBMC) obtained from children with severe OSA and sleep-related CIH.MethodsTen children with OSA (cases) and 5 age-matched children without OSA (controls) were recruited for study. Samples of plasma and PBMC were obtained before and after adenotonsillectomy. The levels of the inflammatory cytokines, interleukin (IL)-1β, IL-6, IL-8, IL-10, IL-12p70, and tumor necrosis factor-α (TNFα), were measured in both plasma and ex vivo culture supernatants of PBMC incubated with lipopolysaccharide (LPS) using the cytometric bead assay.ResultsUpon activation of PBMC by LPS, the levels of IL-8 in the culture supernatants from cases were threefold higher than in controls. The levels of the other cytokines including IL-1β, IL-6, and TNFα, in culture supernatant of PBMC from cases showed no difference from controls; nor were there significant differences in plasma cytokine levels.ConclusionWe speculate that in young children with sleep-related CIH, an enhanced production capacity of IL-8 precedes the development of systemic inflammatory markers. Future work should evaluate IL-8 production capacity as a potential biomarker for OSA severity.

Highlights

  • Severe obstructive sleep apnea (OSA) is characterized by repetitive episodes of disrupted breathing during sleep and recurrent decreases in blood oxygen saturation [1]

  • chronic intermittent hypoxia (CIH) can lead to systemic inflammation in animal models and in patients with Obstructive sleep apnea (OSA) [8,9,10]

  • As DI4 is highly correlated with apnea–hypopnea index (AHI) [17], the values reported for cases in Table 1 as well as the clinical evaluation support a diagnosis of severe OSA

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Summary

Introduction

Severe obstructive sleep apnea (OSA) is characterized by repetitive episodes of disrupted breathing during sleep and recurrent decreases in blood oxygen saturation [1]. A hallmark of severe OSA is sleep-related chronic intermittent hypoxia (CIH). CIH can lead to systemic inflammation in animal models and in patients with OSA [8,9,10]. In both adult and pediatric patients, an upregulation of prototypic inflammatory cytokines such as tumor necrosis factor-α (TNFα) and interleukin-6 (IL-6), arising from activation of the nuclear factor κB (NFκB) pathway, is reported in OSA [11]. Monocytes are known to be altered by chronic hypoxia In this prospective study, we investigated inflammatory cytokine profiles from cultures of peripheral blood mononuclear cells (PBMC) obtained from children with severe OSA and sleep-related CIH

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