Stress Related Shift Toward Inflammaging in Cosmonauts After Long-Duration Space Flight
Stress Related Shift Toward Inflammaging in Cosmonauts After Long-Duration Space Flight
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DOI：
10.3389/fphys.2019.00085
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发表时间：
2019-02-19
影响因子：
4
通讯作者：
Chouker, Alexander
中科院分区：
文献类型：
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作者：
Buchheim, Judith-Irina;Matzel, Sandra;Chouker, Alexander
太空飞行会对人类施加一系列特定的压力源，这些压力源可以调节免疫系统。该机制仍有待阐明，从长远来看对宇航员的影响尚不清楚。目前的大部分研究源于短期太空飞行以及由于操作限制而进行的飞行前和飞行后分析。对参与长期（> 140 天）太空飞行任务的 12 名宇航员的免疫功能在飞行前、飞行后和飞行中的两个时间点进行了监测。虽然唾液中的皮质醇等经典的压力标志物没有显着改变，但内源性大麻素系统（ECS）的血液浓度被发现在飞行中大幅增加，表明存在生物压力反应。此外，受试者的白细胞计数显着增加。着陆后不久，中性粒细胞、单核细胞和 B 细胞增加了 50%，而 NK 细胞则下降了近 60%。血涂片分析显示，淋巴细胞百分比虽然在飞行前和飞行后没有变化，但在飞行中有所升高。地面功能测试显示细胞谷胱甘肽水平稳定，基线未改变，中性粒细胞中的ROS释放受到刺激，但飞行后L-选择素的脱落增加。用真菌抗原对全血样本进行体外刺激显示出高度放大的 TNF 和 IL-1 β 反应。此外，飞行后观察到CD4(+)CD25(+)CD27(l)(ow)调节性T细胞显着减少，但一个月后恢复到正常水平。与此同时，飞行中高水平的调节性细胞因子 TGF-1β、IL-10 和 IL-1ra 在返回地球后迅速下降。最后，我们观察到 CD8(+) T 细胞库向 CD8(+) 记忆细胞的转变，这种转变在返回地球后甚至持续了一个月。结论：长时间的太空飞行引发了内源性大麻素的持续压力依赖性释放，并结合了异常的免疫激活，模仿了患有炎症相关疾病风险的人的特征。返回地球后 30 天，这些影响仍然持续存在。目前可用的飞行中测试以及飞行后观察期需要扩大，以解决这些免疫变化的根本机制和后果，以便根据未来行星际空间探索的个性化方法制定相应的缓解策略。
Space flight exerts a specific conglomerate of stressors on humans that can modulate the immune system. The mechanism remains to be elucidated and the consequences for cosmonauts in the long term are unclear. Most of the current research stems from short-term spaceflights as well as pre- and post-flight analyses due to operational limitations. Immune function of 12 cosmonauts participating in a long-duration (> 140 days) spaceflight mission was monitored pre-, post-, and on two time-points in-flight. While the classical markers for stress such as cortisol in saliva where not significantly altered, blood concentrations of the endocannabinoid system (ECS) were found to be highly increased in-flight indicating a biological stress response. Moreover, subjects showed a significant rise in white blood cell counts. Neutrophils, monocytes and B cells increased by 50% whereas NK cells dropped by nearly 60% shortly after landing. Analysis of blood smears showed that lymphocyte percentages, though unchanged pre- and post-flight were elevated in-flight. Functional tests on the ground revealed stable cellular glutathione levels, unaltered baseline and stimulated ROS release in neutrophils but an increased shedding of L-selectin post-flight. In vitro stimulation of whole blood samples with fungal antigen showed a highly amplified TNF and IL-1 beta response. Furthermore, a significant reduction in CD4(+)CD25(+)CD27(l)(ow) regulatory T cells was observed post-flight but returned to normal levels after one month. Concomitantly, high in-flight levels of regulatory cytokines TGF-1 beta, IL-10 and IL-1ra dropped rapidly after return to Earth. Finally, we observed a shift in the CD8(+) T cell repertoire toward CD8(+) memory cells that lasted even one month after return to Earth.Conclusion: Long-duration spaceflight triggered a sustained stress dependent release of endocannabinoids combined with an aberrant immune activation mimicking features of people at risk for inflammation related diseases. These effects persisted in part 30 days after return to Earth. The currently available repertoire of in-flight testing as well as the post-flight observation periods need to be expanded to tackle the underlying mechanism for and consequences of these immune changes in order to develop corresponding mitigation strategies based on a personalized approach for future interplanetary space explorations.