Abstract
A comprehensive understanding of spaceflight factors involved in immune dysfunction and the evaluation of biomarkers to assess in-flight astronaut health are essential goals for NASA. An elevated neutrophil-to-lymphocyte ratio (NLR) is a potential biomarker candidate, as leukocyte differentials are altered during spaceflight. In the reduced gravity environment of space, rodents and astronauts displayed elevated NLR and granulocyte-to-lymphocyte ratios (GLR), respectively. To simulate microgravity using two well-established ground-based models, we cultured human whole blood-leukocytes in high-aspect rotating wall vessels (HARV-RWV) and used hindlimb unloaded (HU) mice. Both HARV-RWV simulation of leukocytes and HU-exposed mice showed elevated NLR profiles comparable to spaceflight exposed samples. To assess mechanisms involved, we found the simulated microgravity HARV-RWV model resulted in an imbalance of redox processes and activation of myeloperoxidase-producing inflammatory neutrophils, while antioxidant treatment reversed these effects. In the simulated microgravity HU model, mitochondrial catalase-transgenic mice that have reduced oxidative stress responses showed reduced neutrophil counts, NLR, and a dampened release of selective inflammatory cytokines compared to wildtype HU mice, suggesting simulated microgravity induced oxidative stress responses that triggered inflammation. In brief, both spaceflight and simulated microgravity models caused elevated NLR, indicating this as a potential biomarker for future in-flight immune health monitoring.
Highlights
Spaceflight can pose novel challenges to the health of astronauts
Peripheral white blood cell (WBC) data from previously space-flown rodent and astronaut experiments were re-analyzed to determine the contribution of spaceflight to neutrophil-to-lymphocyte ratio (NLR) and granulocyte-tolymphocyte ratios (GLR) immune profile shifts
Health risks that arise from immune dysfunction are complex and include an inability to defend against pathogens, altered tolerance to self-antigens resulting in potential autoimmunity development, chronic inflammation, and immune senescence
Summary
Spaceflight can pose novel challenges to the health of astronauts. For instance, physiological aging occurs significantly faster as a result of spaceflight, when measured by muscle wasting, loss of bone density, and immune dysfunction [1, 2]. Redox imbalance results from a disproportionate increase in reactive. Spaceflight Elevates NLR oxygen species (ROS) produced by the mitochondria [10] compared to antioxidants in the cell. Elevated ROS is a product of the oxidative burst response of neutrophils [11]. Terminally differentiated neutrophils in circulation become activated and engage the oxidative burst response, producing inflammatory mediators [11]. If left unchecked, elevated ROS can cause cellular damage that potentiates inflammation both on Earth and during spaceflight [4, 12]. It is necessary to maintain tight regulation of the oxidative burst response to limit inflammation [13] and regulate immunity during prolonged spaceflight
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