DOI: 10.1161/circ.148.suppl_1.171 ISSN: 0009-7322

Abstract 171: Hyperoxia Potentiates Pro-Inflammatory Immune Cell Activation in vitro

Tyler Rolland, Daniel Cucinotta, Sumbule Zahra, Brian R Weil
  • Physiology (medical)
  • Cardiology and Cardiovascular Medicine

Objective: Supplemental oxygen (O 2 ) is commonly administered to critically ill patients to prevent hypoxemia, but there is growing evidence that hyperoxemia may be an equally deleterious physiological insult. Given the key role of immune activation in critical illness, we investigated whether oxygen tension influences the leukocyte response to pro-inflammatory stimuli in vitro .

Methods: Naïve peripheral blood mononuclear cells (PBMCs) from healthy swine (n=12) were cultured at 10% O 2 (hyperoxia, n = 4), 5% O 2 (physoxia, n = 4), or 3% O 2 (hypoxia, n = 4) for 24 hours with and without lipopolysaccharide (LPS), mitochondrial DNA (mtDNA), or plasma collected from swine 1 hour following resuscitation from sudden cardiac arrest (post-SCA). Leukocyte activation was assessed via TNFα release (ELISA) and inflammatory surface marker expression (flow cytometry), and compared to basal media, transfection control, or pre-SCA plasma, respectively.

Results: Hyperoxia significantly increased PBMC TNFα release in response to LPS, mtDNA, and post-SCA plasma compared to each respective control ( Figure). In contrast, stimulated TNFα release was blunted (SCA plasma) or comparable (LPS and mtDNA) to that observed at physoxia. Consistent with these results, hyperoxia increased PBMC expression of inflammatory surface markers (CD163, CD172, CD14, and CD16) across all conditions, while less pronounced changes were evident after hypoxia.

Conclusions: Hyperoxia potentiates TNFα release and shifts PBMCs towards an activated phenotype in the presence of several pro-inflammatory stimuli, including LPS, mtDNA, and plasma collected following resuscitation from SCA. These findings indicate that leukocyte activation is oxygen tension-dependent and suggest that hyperoxemia should be avoided in critically ill patients to minimize the risk of an excessive inflammatory response.

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