Sleep deprivation predisposes allergic mice to neutrophilic lung inflammation

J Allergy Clin Immunol. 2018 Mar;141(3):1018-1027.e4. doi: 10.1016/j.jaci.2017.06.025. Epub 2017 Jul 19.


Background: 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.

Objective: We sought to evaluate the influence of SD on allergen-induced pulmonary inflammation.

Methods: 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.

Results: 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 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 to corticosteroid treatment in contrast to the allergic group with HS.

Conclusion: Collectively, our data show that sleep quality participates in the progression of allergen-induced eosinophilic lung inflammation to corticosteroid-refractory neutrophilic manifestation.

Keywords: IL-17; Sleep deprivation; airway neutrophilia; allergic lung inflammation; mouse model.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cytokines / genetics
  • Cytokines / immunology
  • Disease Susceptibility
  • Female
  • Humans
  • Hypersensitivity / genetics
  • Hypersensitivity / immunology*
  • Hypersensitivity / pathology
  • Inflammation / genetics
  • Inflammation / immunology
  • Inflammation / pathology
  • Mice
  • Mice, Knockout
  • Pneumonia / genetics
  • Pneumonia / immunology*
  • Pneumonia / pathology
  • Sleep Deprivation / genetics
  • Sleep Deprivation / immunology*
  • Sleep Deprivation / pathology
  • Th17 Cells / immunology*
  • Th17 Cells / pathology


  • Cytokines