The immune system in space

and microgravity
GERALD SONNENFELD
Department of Microbiology, Biochemistry and Immunology, Morehouse School of Medicine, Atlanta, GA

ABSTRACT
SONNENFELD, G. The immune system in space and microgravity. Med. Sci. Sports Exerc., Vol. 34, No. 12, pp. 20212027, 2002.
Space flight and models that created conditions similar to those that occur during space flight have been shown to affect a variety of
immunological responses. These have primarily been cell-mediated immune responses including leukocyte proliferation, cytokine
production, and leukocyte subset distribution. The mechanisms and biomedical consequences of these changes remain to be established.
Among the possible causes of space flight-induced alterations in immune responses are exposure to microgravity, exposure to stress,
exposure to radiation, and many more as yet undetermined causes. This review chronicles the known effects of space flight on the
immune system and explores the possible role of stress in contributing to these changes. Key Words: EXTRATERRESTRIAL
CONDITIONS, RESISTANCE TO INFECTION, STRESS

T
he ability to visit space for longer periods of time has
opened up new aspects of research to determine the
effects of space flight on numerous physiological
functions. Among those being explored is the effects of
space flight on the immune system (71). The purpose of this
review will be to explore the history of the study of the
effects of space flight on immunity. Because more oppor-
tunities have existed to determine the effects of space flight
on immune responses of animals, the main focus of the
review will be on animal models. Finally, a newly emerging
area of the interaction of the immune system with the
neuroendocrine system during space flight will be explored.
SPACE FLIGHT AND IMMUNITY
One of the important regulatory biology interactions af-
fected by space flight is the regulation of the immune
response. Alterations in the regulation of immunity could
have profound effects on the ability of the host to resist
infection and tumors. Reports on the effects of space flight
on the immune system have been interesting but not defin-
itive (17,40,58,65,77 80). These studies have been limited
by the small sample size, the relatively small number of
flights available for immunological studies, and by experi-
mental conditions (17,40,58,65,77 80). Nevertheless, it is
now apparent that several alterations of immunological pa-
Address for correspondence: Gerald Sonnenfeld, Ph.D., Department of
Microbiology, Biochemistry and Immunology, Morehouse School of Med-
icine, 720 Westview Drive, S.W., Atlanta, GA 30310-1495; E-mail:
sonneng@msm.edu.
Submitted for publication February 2002.
Accepted for publication June 2002.
0195-9131/02/3412-2021/$3.00/0
MEDICINE & SCIENCE IN SPORTS & EXERCISE
Copyright 2002 by the American College of Sports Medicine
DOI: 10.1249/01.MSS.0000039073.04569.B5
2021
rameters do occur as a result of space flight. Several factors
could contribute to those effects, including microgravity,
stress, and radiation (17,40,58,65,77 80). It has been diffi-
cult to determine the relative contribution of each one of
those factors to alterations in immunological parameters
induced by space flight. Most importantly, although it is
clear that immune responses change, the possible effects of
space flight on actual resistance to infection have not been
established.
Several studies in rats flown in space have indicated that
prolonged space flight resulted in hypoplasia of lymphoid
organs and alterations in mitogen-induced blastogenesis
(17,40). These effects were transient and returned to normal
after a postflight recovery period (17,40). Data obtained
from human studies showed that there was inhibition of
mitogen-induced blastogenesis of lymphocytes obtained
from astronauts and cosmonauts after the Apollo-Soyuz test
project, Skylab, Space Shuttle, and various Soviet flights
(29,77 80). In these cases, the lymphocytes were obtained
from the crew after their return flight. Samples taken from
the crews as late as 7 d postflight indicated that the blasto-
genic response had not returned to normal. The defects in
immune function may have been due to inhibition of mac-
rophage function, but this has not been confirmed (78 80).
Soviet/Hungarian studies have also indicated that some
cosmonauts had a severe decrease in the ability of their
leukocytes to produce interferon-/ (an important cytokine
that is both antiviral and immunoregulatory) when their
blood was sampled and tested immediately after return from
flight (75). Fifteen of 29 Apollo crew members developed
bacterial or viral infections during their missions or imme-
diately after return during the first week after recovery (24).
The infectious agents included influenza viruses, Pseudo-
monas aeruginosa, and -hemolytic streptococci (24). In
the Apollo 13 mission, one crew member developed a uri-
nary tract infection with P. aeruginosa during the flight
(76). It is possible that the changes in immune responses
induced by space flight (changes in cytokine production
capacity in particular) could have contributed to decreased
resistance to infection.
Human studies have indicated space-flightinduced
changes in human cell culture activities such a leukocyte
blastogenesis (3,1214) and signal transduction in leuko-
cytes (34,56). Studies have also indicated that space flight
alters leukocyte distribution (41,42,74), interferon and other
cytokine production (16), and natural killer cell activity in
humans when measured after flight. Interferon-/ produc-
tion was found to be dramatically enhanced when cultures of
leukocytes were flown and stimulated in space (75). Inter-
estingly, these were the cells from the same cosmonauts
who were tested upon return to earth and shown to have
inhibited interferon production (75). When assessed during
flight, delayed hypersensitivity responses to common recall
antigens are inhibited during both short-term (81) and long-
term (20) space flights. Models of space flight such as
isolation and long-term bed rest with head-down tilt have
resulted in alterations of cytokine production and leukocyte
function (55,57,67). As demonstrated with the interferon,
some of these results have shown opposing results in dif-
ferent flight experiments, i.e., in one experiment an immune
parameter is decreased, and in another it is unaltered or
increased. This is probably due to specific experimental
conditions, in vivo vs in vitro experiments, species of ex-
perimental subject, and complicating additional variables
that occur. Nevertheless, it is clear that exposure to space-
flight conditions dramatically affects the immune system. A
recent study has shown that exposure of humans to sleep
deprivation, which can occur during space flight, results in
alterations of TNF- receptors and interleukin-6 levels in
serum (61).
Studies involving antibody responses have been much
more limited. Short-term space flight has resulted in no
change in total immunoglobulin levels (82), whereas long-
term space flight has shown a small increase in total immu-
noglobulin levels (29). Interestingly, a recent study has
shown no effect of exposure on an Antarctic winter-over
model of isolation in the ability of human subjects to mount
an antibody response to bacteriophage X-174 (60). There-
fore, antibody responses may not be as sensitive to space
flight or models of some components of space-flight con-
ditions as are cell-mediated immune responses.
As a result of the limited opportunities for space flight,
animal models have been used to study changes in immune
responses. Immune responses of rodents have been the main
subject of the studies. Cultures of rodent cells flown in space
have shown altered cytokine production (7) and macrophage
hematopoiesis and function (2). Chapes and associates (8)
found enhanced secretion of several cytokines, including
interferons- and -, interleukin-1, and tumor necrosis fac-
tor-, after murine cells were cultured and challenged to
produce the cytokines during space flight. This is in accor-
dance with results of Talas and associates (75), who found
similar results using human cells. However, the ability of the
tumor necrosis factor to kill cells was inhibited during space
flight (83). This again suggests that some of the contradic-
2022 Official Journal of the American College of Sports Medicine
tory results on the effects of space flight on the immune
system are due to the experimental conditions and parame-
ters observed.
Mice were maintained in a space cabin environment in
which barometric pressure was altered (19). These confined
mice were more susceptible to mengovirus infection than
were controls. These data suggested that maintenance of
mice in this restricted environment with alterations in pres-
sure could have resulted in alterations in immune responses
that decreased their resistance to viral infections. By far, the
most widely used model to simulate some aspects of weight-
lessness that occurs during space flight has been antiortho-
static (1520 head-down tilt), hypokinetic, hypodynamic
suspension (no load on the hind limbs) (AOH). AOH sus-
pension has been carried out either by tail (26,46) or by
harness (47), but immunological results have been similar
using both forms of suspension. The suspension model
allows the development of physiological changes in muscle,
bone, fluid shifts, and other parameters that are similar to
some changes observed after weightlessness during space
flight (46,47). Rats suspended in this model have shown
involution of the thymus similar to that seen after space
flight (17,73). No effect of suspension of rats on levels of
immunoglobulin classes was observed (6), which is similar
to the lack of effect of space flight on levels of circulating
immunoglobulin classes of astronauts (82). Therefore, de-
spite the obvious limitations of the model for simulating
some of the effects of weightlessness seen during space
flight, it has been useful in aiding the determination of
which immunological parameters should be studied in rare
flight experiments.
In our laboratory, we began our studies on the effects of
space flight on immune responses by using the AOH sus-
pension model. We utilized both the rat tail and harness
suspension systems, and also developed a new mouse har-
ness suspension model (72). Suspension of mice in the new
model resulted in physiological changes that were similar to
those observed using the rat suspension model (72). The
first series of experiments we carried out involved the study
of cytokines. Cytokines are soluble, non-antibody mediators
that play a major role in cell-to-cell communication and
regulation of immune responses (5). The first group of
cytokines we studied was the interferons. Interferons are a
family of proteins that have antiviral activity and several
other activities, including regulation of immune responses
(5). Interferon- is produced primarily by leukocytes after
stimulation with viruses, double-stranded RNA, or other
nonspecific inducers (5). Interferon- is produced primarily
by fibroblasts by the same stimuli as interferon- (5). In
many cases, they are difficult to separate and are referred to
commonly as interferon-/. The third type of interferon is
interferon-. Interferon- is a product of an immune re-
sponse by T-lymphocytes stimulated either with specific
antigen or with a mitogen such as concanavalin-A or by
natural killer cells (5).
The next studies performed by our laboratory showed that
suspension of rats in an AOH model resulted in severe
inhibition of interferon-/ production (63). The rats were
http://www.acsm-msse.org
suspended antiorthostatically in this tail suspension model
for 2 wk and then challenged intravenously with polyriboi-
nosinic-polyribocytidylic acid (poly-I:C, a double-stranded
RNA inducer of interferon-/. There was an 80% decrease
in interferon-/ production compared with normally caged
controls (63). In more recent studies, rats were suspended
antiorthostatically for 12 wk, and spleens were removed
immediately after the rats were taken down from suspen-
sion. These results suggest that antiorthostatic suspension of
rats resulted in altered interferon production, a finding sim-
ilar to that observed when cosmonauts were tested for in-
terferon production after space flight (75).
Similar results were observed when mice were suspended
antiorthostatically (53). Using the mouse model, we were
able to add a control for orthostatic suspension. In this
control for the stress of confinement and stress of suspen-
sion, mice were suspended in a harness with no head-down
tilt. Mice suspended for 12 wk in the antiorthostatic ori-
entation showed severely inhibited interferon-/ produc-
tion compared with normally housed controls (53). Mice
suspended in the orthostatic orientation showed no change
in interferon-/ production compared with controls (53).
This suggested that the antiorthostatic orientation of suspen-
sion was required for inhibited interferon / production,
i.e., the stress of suspension alone could not account entirely
for inhibited interferon production. Mice suspended anti-
orthostatically and then allowed to recover in normal caging
for 1 wk regained their capacity to produce interferon-/
(53). A more recent study carried out in our laboratory has
also indicated that interferon- production can be altered by
antiorthostatic suspension (4).
An additional suspension study using mice was carried
out by Fleming and associates (18). In this study, they
showed that mice suspended antiorthostatically had im-
paired ability to produce superoxide, decreased ability to kill
phagocytosed bacteria (Propionibacterium acnes), and al-
tered corticosterone levels that did not correlate with im-
munosuppressive effects of suspension (18). This indicated
that antiorthostatic suspension could alter the inflammatory
and phagocytic responses of the host. These data were not
substantiated by others, who demonstrated no effect in a rat
suspension model (44). The apparently contradictory data
regarding suspension effects on inflammatory responses and
phagocytosis raises a theme that was previously described
regarding space-flight experiments. Sometimes, results ap-
pear to be contradictory. This is probably due to specific
experimental conditions and complicating additional vari-
ables that occur.
In addition, we used the model to determine whether
suspension resulted in alterations to resistance to infection.
Female Swiss/Webster mice were inoculated with the D
variant of encephalomyocarditis virus (EMC-D virus).
EMC-D virus is a convenient virus to utilize, because al-
teration in a glucose tolerance test is all that is necessary to
show successful infection with the virus. Females of the
Swiss/Webster strain of mouse are normally resistant totally
to infection with EMC-D virus (22). Resistance to EMC-D
virus is mediated, at least in part, by interferon (22). Anti-
IMMUNITY AND SPACE
orthostatically suspended mice became susceptible to infec-
tion, whereas orthostatically suspended mice remained re-
sistant (22). Alterations in resistance to EMC-D virus
correlated with alterations in interferon production. There-
fore, antiorthostatic suspension-induced changes in inter-
feron production could have contributed to the compro-
mised resistance to EMC-D virus infection. This raises the
possibility that changes in the immune systems that occur
during or after space flight could contribute to possible
compromised resistance to infectious diseases. These results
indicated that changes in immunological parameters in-
duced by antiorthostatic suspension had the potential to alter
resistance to infection.
In view of the above findings, we had the opportunity to
plan our first flight studies. Several rats were flown in
SpaceLab-3, and experiments were carried out to determine
the effects of flight on cytokine production (21). The rats
were flown in the Space Shuttle for 7 d, and after landing,
a transcontinental airplane flight and a 12-h delay occurred
before sacrifice. This delay and flight could have affected
the results we obtained. After sacrifice, spleens were re-
moved from the rats and place in individual cell culture. The
cultures were then challenged with concanavalin-A to in-
duce interferon-. After the appropriate time interval, the
cultures were harvested and assayed for interferon- activ-
ity. Interferon- production was reduced significantly in
cells taken from rats immediately after flight, compared
with cells from control rats (21). This flight experiment
yielded a result similar to that observed after antiorthostatic
suspension of rats and consistent with the impaired inter-
feron production by cosmonauts after flight (75).
Production of another cytokine, interleukin-3, was also
measured in the same experiment on SpaceLab-3 used for
production of interferon- (21). Interleukin-3 plays a major
role as a growth factor for immunologically important cells.
In this case, cells from rats flown in SpaceLab-3 showed the
same pattern of production of interleukin-3 as did cells from
control rats (21). These data suggested that not all immu-
nological parameters are affected equally by space flight.
We were also fortunate to be able to participate in the
Cosmos #1887 Soviet space flight (64). In this case, we
extended our studies to other immunological areas. We
carried out experiments to determine the effects of space
flight on the distribution of leukocyte subpopulations. The
distribution of leukocyte subpopulations has been shown to
be an important indicator of normal immunological func-
tion, e.g., patients with acquired immune deficiency syn-
drome (AIDS) have an altered ratio of CD-4 T lympho-
cytes to CD-8 T-lymphocytes (31). In our first set of
experiments, spleens were removed from 5 rats flown for
12.5 d on biosputnik Cosmos #1887. The biosputnik landed
off course, and a 48-h delay and a transcontinental airplane
flight occurred between landing and sacrifice of the rats.
This delay could have affected the results we observed. The
spleens were dissociated into individual cells, and separate
samples were stained with different antibodies directed
against markers on the surface of rat leukocyte populations.
These antibodies were antiasialo GM-1 (natural killer cells),
Medicine & Science in Sports & Exercise 2023
OX-39 (interleukin-2 receptor), OX-1 (pan-leukocyte mark-
er), W3/25 (CD-4 T lymphocyte), OX-8 (CD-8 T-lym-
phocyte), W3/13 (pan T-lymphocyte), OX-4 (polymorphic
la-class II histocompatibility antigen), antirat IgG Fab, an-
tirabbit IgG (irrelevant antibody control), and no antibody
(negative control). The stained cells were then analyzed
using a flow cytometer. Although there may be problems
with nonspecific staining in these results, a trend suggesting
a dramatic shift in the following cell populations compared
with synchronous (rats treated the same way as flight rats
except for actual space flight) and ground controls: T-
lymphocytes, CD-8 T-lymphocytes, and interleukin-2 re-
ceptor-bearing T-lymphocytes (64). The increase in inter-
leukin-2 receptor-bearing T-lymphocytes could have
indicated an increased aberrant immunologic activity in-
duced by space flight. However, this increased activity
could have been held in check by the increased level of
CD8 T-lymphocytes. This altered ratio of T-lymphocyte
subsets could also account for, at least in part, inhibited
blastogenic responses and interferon production reported
previously after space flight and may be related to an altered
TH-1/TH-2 cytokine profile.
Additional studies carried out on rats flown in Cosmos
#1887 involved bone marrow cells. Due to the limited
number of bone marrow cells from the femur made available
to us, only two cell populations were examined in the bone
marrow, i.e., the total leukocyte population and the leuko-
cytes carrying surface immunoglobulin. The analysis
showed a large number of myelogenous cells bearing sur-
face immunoglobulin from flown rats as compared with
synchronous and ground control rats (64). Myelogenous
cells are monocyte/macrophage precursors and would not
have been expected to have a surface immunoglobulin
marker. In addition, the bone marrow cells were also tested
for their ability to respond to macrophage colony stimulat-
ing factor (M-CSF). M-CSF stimulates the division of
monocyte-macrophage precursors (59). The bone marrow
cells from flown rats were inhibited in their ability to form
colonies in the presence of M-CSF, indicating a lack of
division on the part of those precursor cells (64). The data
with the bone marrow cells suggested that an unusual re-
sponse for myelogenous cells to divide while they were still
in the bone marrow of flown rats was induced by space
flight and that those cells were refractory to additional
exogenous stimulation by M-CSF. Monocytes/macro-
phages, therefore, are immunologically important cells that
appear to be affected by space flight.
We were able to repeat the experiments described above
for the Cosmos #1887 flight (64) during the Cosmos #2044
flight in 1990. Analysis of the data suggests a similar pattern
of results to those observed during the Cosmos #1887 flight
for both CSF and leukocyte-phenotyping studies (66). Ad-
ditional studies indicated that natural killer cell activity was
also affected by space flight (54). We participated in an
additional study carried out by A. Lesnyak, using rats that
were euthanized and dissected during a Space Shuttle flight
(33). In this case, rats were euthanized 1 d before landing,
and tissues were kept refrigerated until landing and analysis.
2024 Official Journal of the American College of Sports Medicine
Control animals were euthanized at the same time on the
ground, and tissues were maintained under similar condi-
tions for the same duration as the flight samples. All sam-
ples were analyzed at the same time. Results indicated that
both leukocyte blastogenesis and natural killer cell activity
were inhibited in samples obtained during flight compared
with ground controls (33). This indicates that the actual
in-flight conditions contributed to the effects of space flight
on the immunological parameters observed.
In another study, we carried out an experiment using
pregnant rats flown on the Space Shuttle. Immune responses
of dams, fetuses, and pups (fetuses and pups obtained after
landing) were determined after landing (69). Interferon-
production, leukocyte blastogenesis, and the response of
immature cells to colony-stimulating factor all showed
trends to inhibition in the dams but were unaffected in the
pups and fetuses (when observation was possible) (69).
These results suggest that the limited number of immune
responses we observed in offspring of pregnant rats were not
affected by space flight.
Recent studies have been carried out by Chapes and his
associates (9,10) to determine whether there could be inter-
ventions that could prevent or ameliorate the effects of space
flight on the immune system. In one set of experiments (10),
treatment of rats before and during flight with interleukin-2
was utilized to determine whether detrimental effects of
space flight on the immune system could be ameliorated. In
this case, space-flight conditions induced very small
changes in the immune system of control rats, so the effects
of interleukin-2 were difficult to evaluate. In another exper-
iment, rats were implanted with chambers that released
insulin growth factor-1 and then subjected to space flight
(9). The results suggested that insulin growth factor-1 could
lessen some of the effects of space flight on the immune
system but that space flight can also affect the normal
response to the growth factor. Therefore, amelioration of
space flight effects on immune responses remains an area
that requires extensive future study.
Although most studies carried out in our laboratory and
those of others on the effects of space flight on the immune
system involved the use of rodents, there has been one
limited study involving the use of rhesus monkeys. We were
also able to participate in limited studies with monkeys. In
a Russian Cosmos biosatellite mission, monkeys tested after
return to earth showed decreases in interleukin-1 produc-
tion, alterations in receptors for cytokines, and a decrease in
the ability of bone marrow cells to respond to exogenous
colony-stimulating factors (68). These results are similar to
those observed in studies involving rodents and humans, and
validate the use of the animal models for studying the effects
of space flight on the immune system.
In view of the current limitations on space flight exper-
iments caused by construction of the International Space
Station, we have again focused on AOH suspension as a
potential model for the effects of space flight on immune
responses and resistance to infection. During the Cosmos
2044 flight, a parallel antiorthostatic suspension study was
carried out. In this case, antiorthostatic suspension of rats
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resulted in similar results to those seen after space flight
with regard to the inhibited response of bone marrow cells
to CSF but showed no correlation to the effects of space
flight on subpopulations of leukocytes (66).
Other groups have also carried out studies to determine
the effects of space flight and antiorthostatic suspension on
immune responses. These results are, in general, similar to
our own results on leukocyte subset distribution and com-
partmentalization of the effects of space flight on immune
responses (1,15,23,25,48 50). Additionally, an ability of
the antiorthostatic suspension to model effects of space
flight on dynamic functional immune responses such as
cytokine production but not on nondynamic immune param-
eters such as leukocyte subset distribution has been con-
firmed (1,4,15,23,25,48 50). Pecaut et al. (52) recently
demonstrated that rats flown in space had changes in leu-
kocyte subset distribution and that ground-based modeling
did not show similar results. Therefore, despite its limita-
tions, the antiorthostatic suspension model is a very useful
model for studying the effects of recreating some of the
conditions occurring during space flight on immune re-
sponses and resistance to infection.
To take additional advantage of this model, because it has
not been possible, to date, to carry out studies on the effects
of space flight on resistance to infection, we have carried out
ground-based studies to determine the effects of AOH sus-
pension on resistance of mice to bacterial infection with
Listeria monocytogenes (43,45). We have been able to show
that mice subjected to AOH suspension have enhanced
resistance to primary infection with L. monocytogenes
(43,45). This was probably due to enhanced macrophage
function and cytokine production in eliminating the patho-
gen (43,45). However, at the same time that resistance to
primary infection was enhanced, the ability to generate
long-term immunologic memory to the challenge organism
was decreased after 7 d of suspension (43,45). Therefore,
although initial resistance was enhanced by AOH suspen-
sion, the ability to develop long-term resistance to additional
challenge with infectious organisms was compromised
(43,45).
THE NEUROENDORINE SYSTEM, THE IMMUNE
SYSTEM, AND SPACE FLIGHT
It is well-established that exposure to stress can results in
alterations in immune responses and resistance to infection
mediated by interaction of stress hormones from the sym-
pathetic nervous system and the HPA axis with immune
responses (62). Stress hormones, such as corticosteroids and
catecholamines, have been shown to interact directly with
cells of the immune system and to influence development of
immune responses and the outcome of infections (62). Al-
though such interactions of stress hormones and the immune
system occur, they cannot explain all effects of the stress of
space flight or AOH suspension on the immune system and
resistance to infection (62).
Recently, we have also begun to develop a new approach
to study the effects of the stress of space flight and AOH
IMMUNITY AND SPACE
suspension on resistance to infection. This approach in-
volves the study of the effects of changes in levels of
catecholamines, such as norepinephrine, on the invading
pathogens. The possibility that an infectious organism may
respond to neuroendocrine signals, especially to those that
are elaborated during periods of stress, should not seem that
unlikely. Recent original work by Lyte and his associates
(32,3537) and others establishing this principle has dem-
onstrated that the catecholamines can profoundly influence
the in vitro growth of gram-negative bacteria. Norepineph-
rine, in particular, was shown to increase the growth of
members of the Enterobacteriaceae and Pseudomona-
daceae families by over four logs as compared with bacteria
cultured in control media. In addition to changes in growth,
norepinephrine increased the production of virulence-asso-
ciated factors on a protein equivalent basis as compared with
controls. Production of the Shiga-like toxins by Escherichia
coli 0157:H7 was found to be increased nearly 100-fold in
the presence of norepinephrine (38). Elaboration of the K99
pilus adhesin by the enterotoxigenic E. coli (ETEC) patho-
gen B44, which is responsible for attachment of the bacte-
rium to the intestinal wall, was increased over 1300-fold
(39). Culture of pathogenic bacteria in norepinephrine-con-
taining medium has also led to the discovery by Lyte and
associates (37) of on of the first autoinducers of growth in
bacteria. Importantly, this effect of catecholamines on bac-
terial growth has been shown to be nonnutritional in nature
(32,37).
Studies involving the use of and adrenergic agonists
and antagonists, as well as the less physiologically active
enantiomer of norepinephrine, ()-norepinephrine, sug-
gested that a non-, non- adrenergic receptor-mediated
process may play a role in norepinephrine-induced growth
of gram-negative bacteria (32).
In our laboratory, we have adapted this system to study
additional pathogens (27). We have shown that cat-
echolamines can enhance the growth of Aeromonas hy-
drophila, an opportunistic gram-negative bacterial pathogen
(27). Norepinephrine was the most effective catecholamine
in this system, but epinephrine and dopamine were also
effective (27). We have also shown that a siderophore-type
mechanism may be involved in the interaction of cat-
echolamines with bacteria, but confirmation will require
additional study (28).
Stress can certainly play a role in the effects of space
flight and AOH suspension on immune responses (70).
Stress would not be the only factor involved, as multiple
factors such as radiation exposure, microgravity exposure,
and indirect effects from other body systems such as the
musculoskeletal system could also play a role; however, it
will be important to isolate and identify the effects of stress
on resistance to infection to allow for future development of
specific countermeasures. Although limited evidence to date
suggests that stress hormones such as corticosteroids may
not play a major role in the effects of space flight or AOH
suspension on immune responses (18,30,51), the situation is
unclear with regard to catecholamines, but preliminary ev-
idence does suggest some correlation with space flight-
Medicine & Science in Sports & Exercise 2025
induced effects on immune responses (11). The area has not
been fully or carefully investigated (11), and it is possible
that stress-induced catecholamines could play a role in any
alterations in resistance to infection induced by space flight
or AOH suspension. The effect could be on the host immune
responses or directly on the infectious organisms. This area
should be a potential fruitful subject for future investigation.
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