Oxygen-Dependent Immune and Haemostatic Responses

Oxygen availability is an important regulator of immune, inflammatory, and haemostatic processes. This is particularly relevant to spaceflight, where astronauts may experience hypoxia during reduced-pressure operations or life support emergencies, as well as short periods of hyperoxia during oxygen prebreathing. Therefore, we aimed to explore the effects of oxygen on the immune system and haemostatic responses in mice and humans.

First of all, in this review, we described how hypoxia can both enhance antimicrobial immune responses and activate anti-inflammatory, tissue-protective pathways, providing a framework for understanding how reduced oxygen availability during low-pressure operations or life-support emergencies may influence astronauts’ immune function.

In the first study, short-term hypoxia suppressed pro-inflammatory cytokine responses while increasing adenosine and the anti-inflammatory cytokine IL-10 in mice and healthy volunteers subjected to experimental endotoxemia. This mechanism may influence immune responsiveness during hypoxic exposure associated with reduced-pressure operations or life-support emergencies.

Next, we evaluated the effects of hypoxia on iron metabolism. In healthy volunteers, hypoxia increased erythropoietin and erythroferrone and partially suppressed inflammation-induced hepcidin production. These findings may help explain how hypoxic exposure during low-pressure operations or emergencies could affect iron availability and red-blood-cell production in astronauts.

We also examined haemostatic responses and found that, during experimental systemic inflammation, hypoxia reduced platelet–monocyte interactions and platelet reactivity, without affecting plasmatic coagulation in healthy volunteers. This interaction may be relevant when assessing haemostatic changes during hypoxic exposure in spaceflight.

Finally, we investigated short-term hyperoxia and found that exposure to 100% oxygen did not substantially alter inflammatory cytokine responses in mice or healthy volunteers. These findings are relevant to the brief hyperoxic exposures associated with oxygen prebreathing before spacewalks and other operational uses of supplemental oxygen.

Together, these findings show that changes in oxygen availability can influence immune, inflammatory, erythropoietic, and haemostatic responses, underlining their relevance to astronaut health during different spaceflight conditions.