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Short-term hyperoxia does not exert immunologic effects during experimental murine and human endotoxemia.

Kiers D, Gerretsen J, Janssen E, John A, Groeneveld R, van der Hoeven JG, Scheffer GJ, Pickkers P, Kox M - Sci Rep (2015)

Bottom Line: Here, we demonstrate that, in the absence of systemic inflammation, short-term hyperoxia (100% O2 for 2.5 hours in mice and 3.5 hours in humans) does not result in increased levels of inflammatory cytokines in both mice and healthy volunteers.Furthermore, we show that, compared with room air, hyperoxia does not affect the systemic inflammatory response elicited by administration of bacterial endotoxin in mice and man.Our results indicate that hyperoxia does not exert direct anti-inflammatory effects and temper expectations of using it as an immunomodulatory treatment strategy.

View Article: PubMed Central - PubMed

Affiliation: Department of Intensive Care Medicine, Radboud university medical center, Geert Grooteplein Zuid 10, Nijmegen, 6500 HB, Netherlands.

ABSTRACT
Oxygen therapy to maintain tissue oxygenation is one of the cornerstones of critical care. Therefore, hyperoxia is often encountered in critically ill patients. Epidemiologic studies have demonstrated that hyperoxia may affect outcome, although mechanisms are unclear. Immunologic effects might be involved, as hyperoxia was shown to attenuate inflammation and organ damage in preclinical models. However, it remains unclear whether these observations can be ascribed to direct immunosuppressive effects of hyperoxia or to preserved tissue oxygenation. In contrast to these putative anti-inflammatory effects, hyperoxia may elicit an inflammatory response and organ damage in itself, known as oxygen toxicity. Here, we demonstrate that, in the absence of systemic inflammation, short-term hyperoxia (100% O2 for 2.5 hours in mice and 3.5 hours in humans) does not result in increased levels of inflammatory cytokines in both mice and healthy volunteers. Furthermore, we show that, compared with room air, hyperoxia does not affect the systemic inflammatory response elicited by administration of bacterial endotoxin in mice and man. Finally, neutrophil phagocytosis and ROS generation are unaffected by short-term hyperoxia. Our results indicate that hyperoxia does not exert direct anti-inflammatory effects and temper expectations of using it as an immunomodulatory treatment strategy.

No MeSH data available.


Related in: MedlinePlus

Ex vivo whole blood stimulation in healthy volunteers.(a) Tumor necrosis factor (TNF)α and (b)interleukin (IL)-6 cytokine production in whole blood stimulated exvivo with LPS. Data are expressed as median with interquartilerange. NORM-E: normoxic endotoxemia, HYPER-E: hyperoxic endotoxemia, HYPER:hyperoxia.
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f5: Ex vivo whole blood stimulation in healthy volunteers.(a) Tumor necrosis factor (TNF)α and (b)interleukin (IL)-6 cytokine production in whole blood stimulated exvivo with LPS. Data are expressed as median with interquartilerange. NORM-E: normoxic endotoxemia, HYPER-E: hyperoxic endotoxemia, HYPER:hyperoxia.

Mentions: In the hyperoxia group, ex vivo production of TNFα wasslightly increased at several time-points, but no clear relationship withthe period of hyperoxia was evident (Fig. 5a).Furthermore, IL-6 production was unaffected (Fig. 5b).As circulating monocytes decrease during endotoxemia, ex vivocytokine production could not be assessed one to three hours after LPSadministration. As expected, in both endotoxemic groups leukocyte cytokineproduction capacity was blunted four and eight hours afterLPS-administration due to endotoxin tolerance, which fully recovered thesubsequent day. There were no differences in ex vivo cytokineproduction between the normoxic and hyperoxic endotoxemia groups.


Short-term hyperoxia does not exert immunologic effects during experimental murine and human endotoxemia.

Kiers D, Gerretsen J, Janssen E, John A, Groeneveld R, van der Hoeven JG, Scheffer GJ, Pickkers P, Kox M - Sci Rep (2015)

Ex vivo whole blood stimulation in healthy volunteers.(a) Tumor necrosis factor (TNF)α and (b)interleukin (IL)-6 cytokine production in whole blood stimulated exvivo with LPS. Data are expressed as median with interquartilerange. NORM-E: normoxic endotoxemia, HYPER-E: hyperoxic endotoxemia, HYPER:hyperoxia.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4663498&req=5

f5: Ex vivo whole blood stimulation in healthy volunteers.(a) Tumor necrosis factor (TNF)α and (b)interleukin (IL)-6 cytokine production in whole blood stimulated exvivo with LPS. Data are expressed as median with interquartilerange. NORM-E: normoxic endotoxemia, HYPER-E: hyperoxic endotoxemia, HYPER:hyperoxia.
Mentions: In the hyperoxia group, ex vivo production of TNFα wasslightly increased at several time-points, but no clear relationship withthe period of hyperoxia was evident (Fig. 5a).Furthermore, IL-6 production was unaffected (Fig. 5b).As circulating monocytes decrease during endotoxemia, ex vivocytokine production could not be assessed one to three hours after LPSadministration. As expected, in both endotoxemic groups leukocyte cytokineproduction capacity was blunted four and eight hours afterLPS-administration due to endotoxin tolerance, which fully recovered thesubsequent day. There were no differences in ex vivo cytokineproduction between the normoxic and hyperoxic endotoxemia groups.

Bottom Line: Here, we demonstrate that, in the absence of systemic inflammation, short-term hyperoxia (100% O2 for 2.5 hours in mice and 3.5 hours in humans) does not result in increased levels of inflammatory cytokines in both mice and healthy volunteers.Furthermore, we show that, compared with room air, hyperoxia does not affect the systemic inflammatory response elicited by administration of bacterial endotoxin in mice and man.Our results indicate that hyperoxia does not exert direct anti-inflammatory effects and temper expectations of using it as an immunomodulatory treatment strategy.

View Article: PubMed Central - PubMed

Affiliation: Department of Intensive Care Medicine, Radboud university medical center, Geert Grooteplein Zuid 10, Nijmegen, 6500 HB, Netherlands.

ABSTRACT
Oxygen therapy to maintain tissue oxygenation is one of the cornerstones of critical care. Therefore, hyperoxia is often encountered in critically ill patients. Epidemiologic studies have demonstrated that hyperoxia may affect outcome, although mechanisms are unclear. Immunologic effects might be involved, as hyperoxia was shown to attenuate inflammation and organ damage in preclinical models. However, it remains unclear whether these observations can be ascribed to direct immunosuppressive effects of hyperoxia or to preserved tissue oxygenation. In contrast to these putative anti-inflammatory effects, hyperoxia may elicit an inflammatory response and organ damage in itself, known as oxygen toxicity. Here, we demonstrate that, in the absence of systemic inflammation, short-term hyperoxia (100% O2 for 2.5 hours in mice and 3.5 hours in humans) does not result in increased levels of inflammatory cytokines in both mice and healthy volunteers. Furthermore, we show that, compared with room air, hyperoxia does not affect the systemic inflammatory response elicited by administration of bacterial endotoxin in mice and man. Finally, neutrophil phagocytosis and ROS generation are unaffected by short-term hyperoxia. Our results indicate that hyperoxia does not exert direct anti-inflammatory effects and temper expectations of using it as an immunomodulatory treatment strategy.

No MeSH data available.


Related in: MedlinePlus