Abstract
A major risk for astronauts during prolonged space flight is infection as a result of the combined effects of microgravity, situational and confinement stress, alterations in food intake, altered circadian rhythm, and radiation that can significantly impair the immune system and the body’s defense systems. We previously reported a massive increase in morbidity with a decrease in the ability to control a bacterial challenge when mice were maintained under hindlimb suspension (HS) conditions and exposed to solar particle event (SPE)-like radiation. HS and SPE-like radiation treatment alone resulted in a borderline significant increase in morbidity. Therefore, development and testing of countermeasures that can be used during extended space missions in the setting of exposure to SPE radiation becomes a serious need. In the present study, we investigated the efficacy of enrofloxacin (an orally bioavailable antibiotic) and Granulocyte colony stimulating factor (G-CSF) (Neulasta) on enhancing resistance to Pseudomonas aeruginosa infection in mice subjected to HS and SPE-like radiation. The results revealed that treatment with enrofloxacin or G-CSF enhanced bacterial clearance and significantly decreased morbidity and mortality in challenged mice exposed to suspension and radiation. These results establish that antibiotics, such as enrofloxacin, and G-CSF could be effective countermeasures to decrease the risk of bacterial infections after exposure to SPE radiation during extended space flight, thereby reducing both the risk to the crew and the danger of mission failure.
Highlights
The potential major risk of developing infections due to impaired immune function during prolonged space flight has been a continued concern since the beginning of human spaceflight
We hypothesized that two countermeasures with completely different modes of action could control a bacterial infection in mice subjected to the hindlimb suspension (HS) model of microgravity plus exposure to solar particle event (SPE)-like radiation
An optimal countermeasure would be avoidance of exposure to an SPE, but they cannot be predicted and it is believed that an astronaut may have little or no notice of an incoming SPE
Summary
The potential major risk of developing infections due to impaired immune function during prolonged space flight has been a continued concern since the beginning of human spaceflight. A large literature exists on the impairment of the immune system by spaceflight and model systems that potentially lead to a reduced ability to control a variety of infections (reviewed in [9,12,13]). Space factors shown to potentially impair immune function include microgravity [14,15,16,17], radiation [7], physiological stress [18,19] disruption of circadian rhythms [20,21] and altered nutrition [22]. The first countermeasure used was a broad-spectrum orally available antibiotic (enrofloxacin), and the second countermeasure used was granulocyte colony-stimulating factor (G-CSF, Neulasta) Both were found to be highly effective in preventing morbidity and aiding the clearance of systemic bacteria
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