Department of Microbiology, Immunology and Parasitology, Federal University of São Paulo (UNIFESP/EPM), São Paulo, Brazil.
Department of Psychobiology, Federal University of São Paulo (UNIFESP/EPM), São Paulo, Brazil.
J Allergy Clin Immunol. 2018 Mar;141(3):1018-1027.e4. doi: 10.1016/j.jaci.2017.06.025. Epub 2017 Jul 19.
Although different studies associated sleep deprivation (SD) with systemic inflammatory changes, the effect of sleep duration on the pathology of allergic chronic diseases is poorly understood.
We sought to evaluate the influence of SD on allergen-induced pulmonary inflammation.
Ovalbumin (OVA)-sensitized C57BL/6 mice were exposed to a first set of intranasal OVA challenge under SD or healthy sleep (HS) conditions, followed by a second OVA challenge, 1 week apart. Some groups were subjected to corticosteroid treatment with dexamethasone.
OVA-sensitized mice with SD had more severe airway inflammation than the allergic group with HS. Analysis of lung parenchyma revealed that the inflammation in allergic mice with SD was marked by an influx of neutrophils (mainly) and eosinophils and secretion of IL-6, TNF-α, and IL-17 in contrast to the eosinophilic inflammation and IL-4 production observed in allergic mice with HS. The same cytokine profile was observed in ex vivo culture of cervical lymph node cells and splenocytes, indicating that in allergic mice SD favors immune responses toward a proinflammatory T17 profile. This idea is supported by the fact that disruption of IL-17 signaling (IL-17 receptor A) prevented airway neutrophilia in allergic mice with SD. Furthermore, allergic mice with SD became refractory to corticosteroid treatment in contrast to the allergic group with HS.
Collectively, our data show that sleep quality participates in the progression of allergen-induced eosinophilic lung inflammation to corticosteroid-refractory neutrophilic manifestation.
尽管已有多项研究表明睡眠剥夺（SD）与全身炎症变化有关，但睡眠持续时间对过敏性慢性疾病病理的影响尚不清楚。
我们旨在评估 SD 对变应原诱导的肺部炎症的影响。
卵清蛋白（OVA）致敏的 C57BL/6 小鼠在 SD 或健康睡眠（HS）条件下接受了一组鼻腔内 OVA 挑战，1 周后进行了第二次 OVA 挑战。一些组接受了地塞米松的皮质类固醇治疗。
与 HS 组相比，SD 组的 OVA 致敏小鼠气道炎症更严重。对肺实质的分析表明，SD 组过敏小鼠的炎症以中性粒细胞（主要）和嗜酸性粒细胞的浸润以及白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）和白细胞介素-17（IL-17）的分泌为特征，与 HS 组过敏小鼠中观察到的嗜酸性粒细胞炎症和 IL-4 产生形成对比。SD 组过敏小鼠颈淋巴结细胞和脾细胞的体外培养也观察到了相同的细胞因子谱，表明在 SD 组过敏小鼠中，SD 有利于向促炎 T17 表型的免疫反应。这一观点得到了以下事实的支持：破坏白细胞介素-17 信号（白细胞介素-17 受体 A）可防止 SD 组过敏小鼠的气道中性粒细胞增多。此外，与 HS 组过敏小鼠相比，SD 组过敏小鼠对皮质类固醇治疗产生了耐药性。
总的来说，我们的数据表明，睡眠质量参与了变应原诱导的嗜酸性肺部炎症向皮质类固醇难治性中性粒细胞表现的进展。
