Inflammasome Activation: A Keystone of Proinflammatory Response in Obstructive Sleep Apnea

Am J Respir Crit Care Med. 2022 Jun 1;205(11):1337-1348. doi: 10.1164/rccm.202106-1445OC.


Rationale: As the mechanism that links obstructive sleep apnea (OSA) with the regulation of inflammatory response is not well known, it is important to understand the inflammasome activation, mainly of NLRP3 (nucleotide-binding oligomerization domain-like receptor 3). Objectives: To assess the NLRP3 activity in patients with severe OSA and to identify its role in the systemic inflammatory response of patients with OSA. Methods: We analyzed the NLRP3 activity as well as key components of the inflammasome cascade, such as adaptor molecule apoptosis-associated speck-like protein, caspase-1, Gasdermin D, IL-1β, IL-18, and tissue factor, in monocytes and plasma from patients with severe OSA and control subjects without sleep apnea. We explored the association of the different key markers with inflammatory comorbidities. Measurements and Main Results: Monocytes from patients with severe OSA presented higher NLRP3 activity than those from control subjects, which directly correlated with the apnea-hypopnea index and hypoxemic indices. NLRP3 overactivity triggered inflammatory cytokines (IL-1β and IL-18) via caspase-1 and increased Gasdermin D, allowing for tissue factor to be released. In vitro models confirmed that monocytes increase NLRP3 signaling under intermittent hypoxia in a hypoxia-inducible factor-1α-dependent manner, and/or in combination with plasma from patients with OSA. Plasma concentrations of tissue factor were higher in patients with OSA with systemic inflammatory comorbidities than in those without them. Conclusions: In patients with severe OSA, NLRP3 activation might be a linking mechanism between intermittent hypoxia and other OSA-induced immediate changes with the development of systemic inflammatory response.

Keywords: HIF1α; NLRP3; OSA; intermittent hypoxia; tissue factor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Caspase 1 / metabolism
  • Humans
  • Hypoxia
  • Inflammasomes* / metabolism
  • Interleukin-18
  • Interleukin-1beta / metabolism
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism
  • Sleep Apnea, Obstructive* / complications
  • Systemic Inflammatory Response Syndrome
  • Thromboplastin


  • Inflammasomes
  • Interleukin-18
  • Interleukin-1beta
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Thromboplastin
  • Caspase 1