Ke Danbing, Kitamura Yuji, Lejtenyi Duncan, Mazer Bruce, Brouillette Robert T, Brown Karen
1Research Institute, McGill University Health Center, 1001 Decarie Boulevard, Montreal, QC H4A 3J1 Canada.
2Department of Anesthesia, McGill University Health Center, 1001 Decarie Boulevard, Montreal, QC H4A 3J1 Canada.
Allergy Asthma Clin Immunol. 2019 Apr 16;15:23. doi: 10.1186/s13223-019-0338-1. eCollection 2019.
Obstructive 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.
Ten 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.
Upon 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.
We 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.
阻塞性睡眠呼吸暂停(OSA)是心血管疾病、代谢紊乱和认知功能障碍的危险因素。目前的观点认为慢性间歇性缺氧(CIH)与氧化应激和全身炎症有关。然而,导致儿童OSA相关发病机制的事件顺序尚不清楚。已知单核细胞会因慢性缺氧而发生改变。因此,在这项前瞻性研究中,我们调查了从患有严重OSA和睡眠相关CIH的儿童获得的外周血单核细胞(PBMC)培养物中的炎性细胞因子谱。
招募了10名患有OSA的儿童(病例组)和5名年龄匹配的无OSA儿童(对照组)进行研究。在腺样体扁桃体切除术前和术后采集血浆和PBMC样本。使用细胞计数珠分析法测量血浆和与脂多糖(LPS)孵育的PBMC体外培养上清液中炎性细胞因子白细胞介素(IL)-1β、IL-6、IL-8、IL-10、IL-12p70和肿瘤坏死因子-α(TNFα)的水平。
用LPS激活PBMC后,病例组培养上清液中IL-8水平比对照组高两倍。病例组PBMC培养上清液中包括IL-1β、IL-6和TNFα在内的其他细胞因子水平与对照组无差异;血浆细胞因子水平也无显著差异。
我们推测,在患有睡眠相关CIH的幼儿中,IL-8产生能力增强先于全身炎症标志物的出现。未来的研究应评估IL-8产生能力作为OSA严重程度潜在生物标志物的价值。