Sleep deprivation predisposes allergic mice to neutrophilic lung inflammation

Abstract

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, 1week apart. Some groups were subjected to corticosteroidtreatment 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 exvivo culture of cervical lymph node cells and splenocytes, indicating that in allergic mice SD favors immune responses toward a proinflammatory TH17 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 tocorticosteroid treatment in contrast to the allergic group withHS. Collectively, our data show that sleep quality participates in the progression of allergen-induced eosinophiliclung inflammation to corticosteroid-refractory neutrophilic manifestation.