Sick in Space: Stress Compromises Astronauts’ Immune Systems

ASTRONAUT MICHAEL GERNHARDT ATTACHED TO THE SHUTTLE ENDEAVOR DURING A SPACEWALK IN 1995 (CREDIT: NASA)

Two days before the launch of a routine space shuttle mission, a 47-year-old healthy astronaut submitted a saliva sample and ended up testing positive for the varicella zoster virus — the virus responsible for chickenpox and shingles. This was, to say the least, unexpected. Following chickenpox infection, the varicella zoster virus remains dormant in our nervous system and often doesn’t reactivate in healthy people under 60. So why would it reappear in a 47-year-old who is among the healthiest, most physically fit individuals of our workforce? Furthermore, why would it emerge before launch, before any potential dangers of space even presented themselves?

 

The indications for health risks during (as well as before and after) space flight have been scattered and indirect, but always tend toward dangerous. During the Apollo program of the 60s, more than half of flight crew members reported both inflight and pre-flight illnesses, including respiratory infections, urinary tract infections, gastroenteritis, and skin infections [1]. In response, an initiative formed called the Health Stabilization Program that limited crew contact and exposure to potential pathogens before each mission. Astronaut health improved in subsequent missions, but sicknesses were still reported at a higher rate in astronauts than in the non-spacefaring population [2]. Gingivitis and skin infections occurred in the 70s when the US launched its first space station, Skylab, and such maladies continued on into the Space Shuttle and International Space Station missions.

 

ELECTRON MICROGRAPH SHOWING SALMONELLA TYPHIMURIUM, A POTENTIALLY DANGEROUS PATHOGEN TO ASTRONAUTS IN SPACE. (CREDIT: ROCKY MOUNTAIN LABORATORIES, NIAID, NIH)

These reports hinted at the danger of space to astronauts’ health, but recent research has substantiated it. There seems to be little question now that the immune systems of astronauts become suppressed around the time of space flight. Lymphocytes, white blood cells in the immune system that are called upon to destroy infection, have been reported to exhibit reduced function in astronauts following spaceflight of both short (up to 15 days) and long (up to 6 months) duration [2][3][4]. Such reduced function puts astronauts at risk for autoimmune diseases, allergies, hypersensitivity, and even cancer. Lymphocytes are crucial for the production of natural killer cells, which are responsible for tumor surveillance — an especially important task in the high-energy radiation environment of deep space, which is capable of damaging genetic information and increasing the risk of cancer. Another group of cells shown to be impacted by space flight are phagocytes, our body’s first responders, arriving first at the site of infection and working with lymphocytes to fight it.

 

Interestingly, the cause of this decreased immune function may not be the actual environment of space — the microgravity or radiation — but rather something else entirely. There’s good evidence that it may simply be stress. Studies show that acute stress may enhance immunity, such as during a short space flight, but chronic stress is in fact immunosuppressive [5]. This explains why immune responses similar to those from short space flights are also found during periods of intense exercise [1]. Stress hormones alter the circulation of phagocytes and, in both intense exercisers and short-flight astronauts, actually increase phagocyte levels and thus improve defenses against infection. But long-flight astronauts don’t get the same boost; in fact, it’s the opposite [2]. The stressors of long-term space flight are strong, varied and constant: prolonged, isolated confinement; disrupted nutrition and circadian rhythms; time away from family in a crowded environment; lack of privacy; sleep deprivation. No surprise, then, that studies of individuals in Antarctic isolation showed significant decreases in immune response as well [2][4], even though gravity and radiation aren’t factors. It was all due to stress.

 

Hence the appearance of the zoster virus in the astronaut even before launch [6]. The intense planning and preparation for space flight is in and of itself enough stress to compromise the immune system and open the doors for viruses to reactivate. Stress responses, in the form of elevated stress hormone (e.g. epinephrine, cortisol) levels, have been measured during launch and reentry and correlate with upticks in viral shedding and antibody responses, indicative of viral reactivation [7].

 

What makes things even worse for astronauts, though, is that it’s not a one-sided affair. The reduced defense allows the offense — the bacteria and viruses — to take control of the game, but it seems that at the same time the offense itself is actually bolstered. Strangely enough, bacteria seem to grow and survive more easily in space-like environments.

 

A SIMULATED MICROGRAVITY BIOREACTOR USED AT THE UNIVERSITY OF AMSTERDAM (CREDIT: GREENWALD ET AL., “UNDERSTANDING THE PHYSIOLOGICAL CHANGES FROM MICROGRAVITY; http://chen2820.pbworks.com/w/page/11951455/Growing%20cartilage%20in%20space)

Experiments on bacterial growth in space began as early as 1935, when balloon experiments evaluated bacteria’s ability to survive decreased pressure and increased radiation [8]. Recent experiments in rotating wall vessels that suspend bacterial cultures in gentle fluid orbits, simulating the microgravity environment of space, show that such an environment actually enhances cell growth [8][9]. On top of that, such low-turbulence environments appear to also strengthen the stress resistance and virulence of many bacteria, including Salmonella and E. coli [8][9][10]. These bacteria could inflict not just severe food poisoning, but also urinary tract infections and even typhoid fever at their most virulent.

 

For already-immunocompromised astronauts, this is bad news. Things are working against them in both directions. But it gets worse. In spacecraft and space stations, astronauts are forced to be contained in closed environments when exposed to these bacteria, and thus have little to no ability to quarantine a serious disease outbreak if one were to occur.  There is a zoo of microbial flora populating spacecraft and space stations [11]; indeed, some of these microbes are necessary for the astronauts, critical for waste remediation and water/air purification. And even though the astronauts are among the most healthy individuals on the planet, screened for infectious agents like HIV and tuberculosis, they still harbor sleeping demons — latent viruses and E. coli strains that could turn virulent in times of stress.

 

The myriad microbes present in the space station ecosystem are all changing in various ways during spaceflight: some more virulent and some less, some with accelerated growth and others unchanged. More space flight experiments need to be done to fully evaluate these changes, but such experiments are challenging. Not only are they constrained by limited flight opportunities and the extreme financial costs of launches, but they also rely on specialized hardware that must meet rigorous flight standards. Furthermore, it’s nearly impossible in these experiments to control for the differences in missions, which often vary in stress levels depending on personnel and tasks. That’s why simulated models of space, such as the rotating wall vessel experiments or even underwater experiments, have become more common, but they too are quite expensive to execute and cannot fully replicate the true stress that presents itself for astronauts on actual space flights.

 

All this is particularly pertinent now with declared missions to send humans to the Moon and Mars. Aside from the lower gravity and radiation, the first days on Mars will most likely bring exposure to a variety of as yet unknown immunological and environmental challenges [3]. Can we put ourselves in the shoes of those first explorers and imagine their stress levels? Not as they are about to step foot onto the red planet, but before that — before the complex and harrowing landing onto a strange landscape, before the long and boring trip through the nothingness of space with only the company of your crew, your thoughts, and your hope of a new world to keep you sane, before the launch and burn through our home planet’s heavy atmosphere. Imagine the years of planning, each potential problem endlessly thought out, each task designated and leading to the next; and if one link breaks the whole mission collapses.

 

Of course we pick the best of the best for these missions. But in the end, we’re all only human, and stress will be inextricably linked to the future of space travel. Hopefully our immune systems can keep up.

 

Sean Faulk
Staff Writer, Signal to Noise Magazine
PhD Candidate, Earth, Planetary, and Space Sciences, UCLA

 

References

[1] Stowe, R., et al. Leukocyte subsets and neutrophil function after short-term spaceflight. Journal of Leukocyte Biology 65, 179-186 (1999).

[2] Borchers, A., et al. Microgravity and immune responsiveness: Implications for space travel. Nutrition 18(10), 889-898 (2002).

[3] Crucian, B., et al. Immune system dysregulation following short- vs long-duration spaceflight. Aviation, Space, and Environmental Medicine 79(9), 835-843 (2008).

[4] Sonnenfeld, G., & Shearer, W. Immune function during space flight. Nutrition 18(10), 899-903 (2002).

[5] Dhabhar, F. & McEwen, B. Stress-induced enhancement of antigen-specific cell-mediated immunity. Journal of Immunology 156, 2608-2615 (1996).

[6] Mehta, S., et al. Stress-induced subclinical reactivation of varicella zoster virus in astronauts. Journal of Medical Virology 72, 174-179 (2004).

[7] Mehta, S., et al. Reactivation and shedding of cytomegalovirus in astronauts during spaceflight. Journal of Infectious Diseases 182, 1761-1764 (2000).

[8] Nickerson, C., et al. Low-shear modeled microgravity: a global environmental regulatory signal affecting bacterial gene expression, physiology, and pathogenesis. Journal of Microbiological Methods 54, 1-11 (2003).

[9] Nickerson, C., et al. Microbial responses to microgravity and other low-shear environments. Microbiology and Molecular Biology Reviews 68(2), 345-361 (2004).

[10] Wilson, J., et al. Microarray analysis identifies Salmonella genes belonging to the low-shear modeled microgravity regulon. Proceedings of National Academy of Sciences 99(21), 12807-13812 (2002).

[11] Pierson, D. Microbial contamination of spacecraft. NASA Johnson Space Center (2000). https://ntrs.nasa.gov/archive/nasa/casi.ntrs.nasa.gov/20100036603.pdf