Abstract
A better understanding of the combined impact of different space stressors on human health is urgently warranted, considering the upcoming long-duration missions beyond lower Earth orbit. Therefore, a growing number of particle accelerator facilities implement ground-based set-ups to study the effect of simulated space radiation with simulated psychological or physical stressors. The immune system is highly sensitive to these types of stressors and limited information is currently available on the impact of the complex space radiation environment on the astronauts' immune function. This pilot study presents a first step in the implementation of a ground-based set-up with neutron irradiation, which is considered to be an important secondary component in space radiation fields. The effect of dose rate on immune alterations was studied using the in vitro cytokine release assay. Whole blood samples (n = 8) were exposed to 0.125 or 1 Gy of neutron irradiation (fluence-weighted average energy: 29.8 MeV) at a lower dose rate (LDR) of 0.015 Gy/min and a higher dose rate (HDR) of 0.400 Gy/min. Immediately post-irradiation, blood samples were stimulated with lipopolysaccharide (LPS), heat-killed Listeria monocytogenes (HKLM) or lectin pokeweed mitogen (PWM), and incubated for 24 h. Cell-mediated immunity was examined by analysing interleukin-2 (IL-2), interferon-gamma (IFN-γ), tumour necrosis factor-alpha (TNF-α), and interleukin-10 (IL-10) plasma levels. Stimulants significantly increased all cytokine levels except IL-2, where only PWM induced a significant increase. In general, no statistically significant changes were observed in IL-2, IFN-γ, and TNF-α concentrations at different neutron doses and dose rates when compared to their stimulated, sham-irradiated controls. After PWM-stimulation, IL-10 levels were significantly increased at 0.125 Gy HDR and 1 Gy LDR. In a pooled analysis, the HDR significantly increased IL-2 titres (under PWM-stimulation) and IFN-γ titres (with all stimulants), but significantly decreased TNF-α secretion in unstimulated cultures. Due to the limited sample number, no strong conclusions could be made in this pilot study on the effect of neutron radiation as a single stressor on cytokine secretion in response to different stimuli. However, some interesting trends and dose rate effects were observed, which pave the way for future investigations on the synergistic effects of multiple space stressors on immune cell function.
Highlights
Space travel comprises a unique and complex stress model composed of both physical and psychological stress factors, known to induce a large variety of systemic physiological effects that are proven to be detrimental to astronaut’s health [1,2,3]
To validate the in vitro cytokine release assay used for this pilot study, cytokine titres in the unstimulated samples were compared to the stimulated samples
Non-significant increases in IL-2 concentration were observed after 24-h stimulation with heat-killed Listeria monocytogenes (HKLM) or LPS for 50 and 25% of the donors, respectively
Summary
Space travel comprises a unique and complex stress model composed of both physical (cosmic radiation and microgravity) and psychological stress factors, known to induce a large variety of systemic physiological effects that are proven to be detrimental to astronaut’s health [1,2,3]. New insights and radiobiology data on high-LET radiation effects at low dose rates will improve current risk projections for space exploration and hopefully aid in the development and evaluation of possible countermeasures [47] With this goal, the “Optimization and validation of a unique ground-based in vitro model to study space health effects” (INVEST) project was launched, which aims to implement a ground-based in vitro model to study space health effects at iThemba LABS, with a specific emphasis on neutrons at low doses and low dose rates. The lymphocytes were intentionally stimulated ex vivo to mimic a challenged immune scenario, to monitor the disruptive effect of neutron dose and dose rate on the cytokine release profile This method has been extensively used to study immune system dysregulation in several ex vivo studies related to short and long duration spaceflights and in terrestrial analogues [13, 29, 50, 51]
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