Impact Factor 5.511

Among the world's top 10 most-cited Immunology journals

General Commentary ARTICLE

Front. Immunol., 04 September 2018 | https://doi.org/10.3389/fimmu.2018.02024

Commentary: Immune System Dysregulation During Spaceflight: Potential Countermeasures for Deep Space Exploration Missions

  • 1Bevelacqua Resources, Richland, WA, United States
  • 2Diagnostic Imaging Department, Fox Chase Cancer Center, Philadelphia, PA, United States
  • 3INIRPRC, Shiraz University of Medical Sciences, Shiraz, Iran

A commentary on
Immune System Dysregulation During Spaceflight: Potential Countermeasures for Deep Space Exploration Missions

by Crucian BE, Choukèr A, Simpson RJ, Mehta S, Marshall G, Smith SM, et al. (2018). Front Immunol. 9:1437. doi: 10.3389/fimmu.2018.01437

We read with great interest the paper authored by Crucian et al. “Immune System Dysregulation During Spaceflight: Potential Countermeasures for Deep Space Exploration Missions” that is published in Frontiers in Immunology (1). The authors have addressed the key issue of dysregulation of the immune system in deep space missions and state that the immune system is strongly susceptible to a wide variety of stressors ranging from psychological to physical and local environmental factors (including exposure to oxidative stress and radiation). They also note that on deep space missions, beyond the range of the Earth's protective magnetic field (magnetosphere), factors such as ionizing radiation may increase oxidative stress and change both the rate of DNA damage and the effectiveness of the mechanisms involved in DNA repair. Oxidative stress also can be increased by DNA damage which leads to chronic inflammation and ultimately failure of the functions of the immune system. Although the paper authored by Crucian et al. is well-structured and can be considered as a significant contribution to this field, it has three important shortcomings.

The first shortcoming comes from ignoring the reports indicating that low doses of ionizing radiation [e.g., the normal levels of space radiation inside a well-shielded spacecraft when a large solar particle event (SPE) is not in progress] can reduce the oxidative damage in normal tissues. For example, Scott has previously reported that low dose radiation (LDR) stimulates antioxidant production and protects the organism from oxidative damage (2). Moreover, the authors have not considered that dysregulation of the immune system can be due to factors other than radiation. In this light, even pre-mission stress is reported to be of crucial importance (3, 4). Thus, it is likely that immune parameters are affected by pre-mission stress (5).

Second, the authors suggest that astronauts should be supplied with vitamins E, A, and C “Astronauts need to be adequately supplied with vitamins E, A, and C. Whether provision of larger amounts of these as nutraceuticals will be beneficial for immune function warrants further investigation, on Earth and in space.” The role of vitamin C in deep space missions is more important than reported by Crucian et al. Some evidence show that administration of vitamin C can be effective even after exposure to sparsely ionizing radiation (6, 7). Vitamin C can be introduced as a promising non-toxic, cost-effective, easily available radiation mitigator which can be used hours after a significant irradiation event (e.g., a large SPE) (6).

Finally, the key issue of radioadaptation as a factor that affects the human immune system is not considered in this paper (812). Radioadaptation increases the body's resistance to a high level stressor [e.g., a large SPE or exposure to intense high energy, high atomic number (HZE) particles] after a pre-exposure to a low level stressor [e.g., chronic galactic cosmic radiation] (1114). By referring to reports about the importance of radioadaptation in deep space missions (1518), a 2016 NASA report states it is realistic to expect that cells will be exposed to multiple hits of protons before being traversed by an HZE particle (i.e., induction of radioadaptation) (19). Besides the NASA report, a paper authored by 30 scientists from US, Canada, UK, Russia, and Belgium has also confirmed the key role of biological protection of astronauts (20). The authors state that regarding space, it is important to understand how radioadaptive responses can be induced by exposure to high LET radiation. It worth noting that a pre-exposure to low dose radiation can stimulate the defense mechanisms such as increasing antioxidant levels reducing the endogenous DNA damage, increasing DNA repair capacity, and increasing apoptosis of damaged cells (21).

In summary, the paper by Crucian et al. is an important contribution to studies of the biological effects that can occur during space missions. This commentary adds three additional considerations that should be considered when reviewing the conclusions of Crucian et al. The authors hope that this commentary will further stimulate research in studies of the effects of space radiation and enhance the health and safety of astronauts participating is space missions.

Author Contributions

SM has fully reviewed and criticized the original article, drafted the commentary, reviewed, and approved the final manuscript. JB has also reviewed and criticized the original article, assisted in drafting the commentary, reviewed and approved the final manuscript.

Conflict of Interest Statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

References

1. Crucian BE, Choukèr A, Simpson RJ, Mehta S, Marshall G, Smith SM, et al. Immune system dysregulation during spaceflight: potential countermeasures for deep space exploration missions. Front. Immunol. (2018). 9:1437. doi: 10.3389/fimmu.2018.01437

PubMed Abstract | CrossRef Full Text | Google Scholar

2. Scott BR. Radiation-hormesis phenotypes, the related mechanisms and implications for disease prevention and therapy. J Cell Commun Signal. (2014) 8:341–52. doi: 10.1007/s12079-014-0250-x

PubMed Abstract | CrossRef Full Text | Google Scholar

3. Stowe RP, Sams CF, Mehta SK, Kaur I, Jones ML, Feeback DL, et al. Leukocyte subsets and neutrophil function after short-term spaceflight. J Leukoc Biol. (1999) 65:179–86.

PubMed Abstract | Google Scholar

4. Stowe RP, Sams CF, Pierson DL. Adrenocortical and immune responses following short- and long-duration spaceflight. Aviat Space Environ Med. (2011) 82:627–34. doi: 10.3357/ASEM.2980.2011

PubMed Abstract | CrossRef Full Text | Google Scholar

5. Austin AW, Patterson SM, Ziegler MG, Mills PJ. Plasma volume and flight duration effects on post-spaceflight soluble adhesion molecules. Aviat Space Environ Med. (2014) 85:912–8. doi: 10.3357/ASEM.3959.2014

PubMed Abstract | CrossRef Full Text | Google Scholar

6. Mortazavi SMJ, Sharif-Zadeh S, Mozdarani H, Foadi M, Haghani M, Sabet E. Future role of vitamin C in radiation mitigation and its possible applications in manned deep space missions: survival study and the measurement of cell viability. Phys Med. (2014) 30:e97. doi: 10.1016/j.ejmp.2014.07.278

CrossRef Full Text | Google Scholar

7. Sato T, Kinoshita M, Yamamoto T, Ito M, Nishida T, Takeuchi M, et al. Treatment of irradiated mice with high-dose ascorbic acid reduced lethality. PLoS ONE (2015) 10:e0117020. doi: 10.1371/journal.pone.0117020

PubMed Abstract | CrossRef Full Text | Google Scholar

8. Mortazavi SMJ, Bevelacqua JJ, Fornalski KW, Welsh J, Doss M. Comments on “space: the final frontier-research relevant to mars”. Health Phys. (2018) 114:344–5. doi: 10.1097/HP.0000000000000823

PubMed Abstract | CrossRef Full Text | Google Scholar

9. Bevelacqua JJ, Mortazavi SMJ. Commentary: human pathophysiological adaptations to the space environment. Front Physiol. (2017) 8:1116. doi: 10.3389/fphys.2017.01116

PubMed Abstract | CrossRef Full Text | Google Scholar

10. Mortazavi SM. Space radiobiology and the new era of induced radioresistance: should traditional concepts be moved to science history museums? Technol Health Care (2013) 21:285–9. doi: 10.3233/THC-130732

PubMed Abstract | CrossRef Full Text | Google Scholar

11. Mortazavi SMJ, Cameron JR, Niroomand-rad A. Adaptive response studies may help choose astronauts for long-term space travel. Adv Space Res. (2003) 31:1543–51. doi: 10.1016/S0273-1177(03)00089-9

PubMed Abstract | CrossRef Full Text | Google Scholar

12. Bevelacqua JJ, Welsh J, Mortazavi SMJ. Comments on “An overview of space medicine.” Br J Anaesth. (2018) 120:874–6. doi: 10.1016/j.bja.2017.12.015

CrossRef Full Text | Google Scholar

13. Mortazavi SMJ, Mozdarani H. Deep space missions and the issue of overcoming the problem of space radiation. Int J Rad Res. (2013) 11:199–202.

Google Scholar

14. Mortazavi SMJ, Motamedifar M, Namdari G, Taheri M, Mortazavi AR, Shokrpour N. Non-Linear adaptive phenomena which decrease the risk of infection after pre-exposure to radiofrequency radiation. Dose Response (2014) 12:233–45. doi: 10.2203/dose-response.12-055

PubMed Abstract | CrossRef Full Text | Google Scholar

15. Bhattacharjee D, Ito A. Deceleration of carcinogenic potential by adaptation with low dose gamma irradiation. In vivo (2001) 15:87–92.

PubMed Abstract | Google Scholar

16. Mortazavi S, Cameron J, Niroomand-rad A editors. Is the adaptive response an efficient protection against the detrimental effects of space radiation. In: International Cosmic Ray Conference. Tsukuba (2003).

Google Scholar

17. Elmore E, Lao X, Kapadia R, Swete M, Redpath J. Neoplastic transformation in vitro by mixed beams of high-energy iron ions and protons. Radiat Res. (2011) 176:291–302. doi: 10.1667/RR2646.1

PubMed Abstract | CrossRef Full Text | Google Scholar

18. Rithidech KN, Lai X, Honikel L, Reungpatthanaphong P, Witzmann FA. Identification of proteins secreted into the medium by human lymphocytes irradiated in vitro with or without adaptive environments. Health Phys. (2012) 102:39. doi: 10.1097/HP.0b013e31822833af

CrossRef Full Text | Google Scholar

19. Huff J, Carnell L, Blattnig S, Chappell L, Kerry G, Lumpkins S, et al. Evidence Report: Risk of Radiation Carcinogenesis. NASA (2016).

20. Cortese F, Klokov D, Osipov A, Stefaniak J, Moskalev A, Schastnaya J, et al. Vive la radioresistance!: converging research in radiobiology and biogerontology to enhance human radioresistance for deep space exploration and colonization. Oncotarget (2018) 9:14692–722. doi: 10.18632/oncotarget.24461

PubMed Abstract | CrossRef Full Text | Google Scholar

21. Feinendegen LE. Evidence for beneficial low level radiation effects and radiation hormesis. Br J Radiol. (2005) 78:3–7. doi: 10.1259/bjr/63353075

PubMed Abstract | CrossRef Full Text | Google Scholar

Keywords: space radiation, immune system, countermeasures, deep space missions, radioadaptation

Citation: Bevelacqua JJ and Mortazavi SMJ (2018) Commentary: Immune System Dysregulation During Spaceflight: Potential Countermeasures for Deep Space Exploration Missions. Front. Immunol. 9:2024. doi: 10.3389/fimmu.2018.02024

Received: 24 July 2018; Accepted: 16 August 2018;
Published: 04 September 2018.

Edited by:

Vida Abedi, Geisinger Health System, United States

Reviewed by:

Mikhail Karganov, Research Institute of General Pathology and Pathophysiology, the Russian Academy of Medical Sciences, Russia

Copyright © 2018 Bevelacqua and Mortazavi. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

*Correspondence: S. M. J. Mortazavi, s.m.javad.mortazavi@fccc.edu
http://orcid.org/0000-0003-0139-2774