Psychosomatic Medicine Faster Service from Outside North America
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Article
Right arrow Abstract Freely available
Right arrow Figures Only
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Stowe, R. P.
Right arrow Articles by Barrett, A. D. T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Stowe, R. P.
Right arrow Articles by Barrett, A. D. T.
Related Collections
Right arrow Immunology
Right arrow Infectious Disease
Psychosomatic Medicine 63:891-895 (2001)
© 2001 American Psychosomatic Society

SPECIAL ISSUE: OUTERSPACE RESEARCH

Elevated Stress Hormone Levels Relate to Epstein-Barr Virus Reactivation in Astronauts

Raymond P. Stowe, PhD, Duane L. Pierson, PhD and Alan D. T. Barrett, PhD

From the Department of Pathology (R.P.S., A.D.T.B.), University of Texas Medical Branch, Galveston, TX; and Life Sciences Research Laboratories (D.L.P.), National Aeronautics and Space Administration, Lyndon B. Johnson Space Center, Houston, TX.

Address reprint requests to: Raymond P. Stowe, PhD, Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555-0609. Email: rpstowe{at}bluefin.utmb.edu


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 ACKNOWLEDGMENTS
 REFERENCES
 
OBJECTIVE: The objective of this study was to determine the effects of stress and spaceflight on levels of neuroendocrine hormones and Epstein-Barr virus (EBV)–specific antibodies in astronauts.

METHODS: Antiviral antibody titers and stress hormones were measured in plasma samples collected from 28 astronauts at their annual medical exam (baseline), 10 days before launch (L-10), landing day (R+0), and 3 days after landing (R+3). Urinary stress hormones were also measured at L-10 and R+0.

RESULTS: Significant increases (p < .01) in EBV virus capsid antigen antibodies were found at all three time points (L-10, R+0, and R+3) as compared with baseline samples. Anti-EBV nuclear antigen antibodies were significantly decreased at L-10 (p < .05) and continued to decrease after spaceflight (R+0 and R+3, p < .01). No changes were found in antibodies to the nonlatent measles virus. The 11 astronauts who showed evidence of EBV reactivation had significant increases in urinary epinephrine and norepinephrine as compared with astronauts without EBV reactivation.

CONCLUSION: These findings indicate that physical and psychological stresses associated with spaceflight resulted in decreased virus-specific T-cell immunity and reactivation of EBV.

Key Words: Epstein-Barr virus, • stress, • spaceflight, • microgravity, • viral immunity.

Abbreviations: EBNA = Epstein-Barr virus nuclear antigen;; EBV = Epstein-Barr virus;; ELISPOT = enzyme-linked immunospot assay;; IgG = immunoglobulin G;; L-10 = launch minus 10 days;; R+0 = return/landing day;; R+3 = 3 days after landing;; VCA = viral capsid antigen.


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 ACKNOWLEDGMENTS
 REFERENCES
 
A number of studies have shown that immune function in astronauts is decreased during and after spaceflight. Decreased interferon production, altered distribution of leukocyte and lymphocyte subsets, and decreased delayed-type hypersensitivity have been observed (1–6). It has been proposed that stress may be a major mediating factor in the impaired immune response of astronauts (1, 4, 7). Importantly, stress may result in decreased cellular immunity and predispose individuals to viral infections (8, 9).

To address viral infections in astronauts, we investigated a latent herpesvirus, specifically Epstein-Barr virus (EBV), and its potential as a marker of decreased immune function. EBV remains latent in healthy individuals and undergoes occasional reactivation after primary infection (10). Decreased cellular immunity against EBV permits productive cycles of viral replication, which lead to increased production of EBV lytic antibodies (11). Immunosuppressed individuals also have decreased or absent anti–EBV nuclear antigen (EBNA) antibodies (11–13), which is thought to reflect decreased or absent cytotoxic T-cell function against EBV (14). In support of this interpretation, a positive correlation between anti-EBNA antibody levels and precursor frequency of EBV-specific cytotoxic T-cells has been demonstrated (15). In our initial study, we found increased antibodies to EBV viral capsid antigen (VCA) before flight and 8- to 64-fold increases in EBV early antigen antibodies after spaceflight (16). These findings suggested that chronic stress occurred before flight and that in-flight events (possibly associated with the stress of launch and landing) triggered replication of EBV.

Urinary cortisol and catecholamines were also elevated after flight in this study (16). Elevated levels of cortisol have also been documented during spaceflight (17, 18). Importantly, glucocorticoids downregulate cellular immunity as well as directly reactivate EBV (19–24). The purpose of this study was to measure anti-EBNA antibodies to determine if virus-specific T-cell immunity was decreased. In addition, analyses of the stress hormone data in this study focus on differences between astronauts who showed evidence of EBV reactivation and those who did not.


   MATERIALS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 ACKNOWLEDGMENTS
 REFERENCES
 
Subjects
Three separate samples of peripheral blood were collected from each of the 28 astronauts, all EBV seropositive, who flew aboard five US Space Shuttle flights. The 23 male and 5 female astronauts were between the ages of 36 and 59 years (mean, 42 ± 5 years). The Johnson Space Center Institutional Review Board approved this study, and informed consent was obtained from all subjects before participation.

Design
Peripheral blood was collected in Vacutainer tubes coated with ethylenediaminetetraacetic acid 10 days before launch (L-10), within 4 hours of return/landing (R+0), and 3 days after landing (R+3). Preflight (L-10) and postflight (R+3) blood draws were performed early in the morning (around 7:30 AM) and processed at the Johnson Space Center. Blood collected immediately after spaceflight (R+0) took place at the Kennedy Space Center. Sample collection times at R+0, which varied with the landing time, usually were in the early afternoon. Plasma was obtained after centrifugation and was stored at -70°C until testing. Twenty-four hour urine samples, collected from each crew member at L-10 and R+0, were stored at -20°C until analysis. Baseline anti-viral antibody titer data, routinely measured only once during the astronaut’s first annual medical exam (average of 22 months before flight), were obtained from archived records. Baseline values for anti-VCA antibodies were available for all astronauts; values for anti-measles virus antibodies and anti-EBNA antibodies were available for only 14 and 16 crew members, respectively. Peripheral blood was also drawn 15 days apart on 14 healthy subjects (6 men and 9 women, mean age = 33 ± 6 years) for comparison with the astronauts’ results.

Measurement of Antiviral Antibody Titers
The measurement of anti-VCA IgG antibody titers and anti-measles virus IgG antibody titers has been described in detail (16). Commercially prepared substrate slides and control sera were used for determining antibody titers to EBNA IgG (Bion Enterprises, Park Ridge, IL). Serum samples were first heated at 56°C for 30 minutes to inactivate endogenous complement. Sera was then added to the spot slides, and the slides were incubated at 37°C for 30 minutes and then washed for 5 minutes in phosphate-buffered saline. Guinea pig complement (Colorado Serum Company, Denver, CO) was quickly thawed, diluted 1:10 in cold phosphate-buffered saline, and pipetted onto the spot slides. After a second incubation (37°C for 30 minutes), the slides were washed, and one drop of anti-guinea pig complement fluorescein conjugate was applied to each well of the slide. A final incubation of 37°C for 30 minutes was performed, and then the slides were washed and mounted. The slides were then examined and evaluated by fluorescence microscopy. Two-fold dilutions of plasma or serum from each subject were prepared, and the endpoint titer was determined as the highest dilution still able to demonstrate immunofluorescence-positive cells. All specimens were batch analyzed and read blind-coded.

Measurement of Stress Hormones
The measurement of hormones and immunoglobulins has been described previously in detail (8, 21). Plasma and urinary cortisol were measured by radioimmunoassay. Urinary catecholamines (epinephrine and norepinephrine) were measured by high-performance liquid chromatography. Samples were batch analyzed to minimize interassay variation.

Statistical Analysis
Normality was assessed using the Kolmogorov-Smirnov normality test. Data not normally distributed were subjected to natural log transformations to normalize the distributions before analyses. Because the method of doubling dilutions was used to obtained antibody titer results, a log base-2 transformation was used to reduce variance for statistical comparisons. The natural logarithms of plasma cortisol, urinary epinephrine, and norepinephrine passed the normality test and were used for paired t test statistical analysis. The nonparametric Wilcoxon signed-rank test was used for urinary cortisol, which did not pass even after transformation. Repeated-measures analysis of variance was used to analyze anti-EBNA IgG, anti-VCA IgG, and anti-measles IgG across multiple time points. The percentage of change in each hormone for each subject was calculated as follows: [(R+0 level - L-10 level)/L-10 level] x 100. Statistically significant differences between groups were assessed by the Fisher exact test. Results are expressed as mean ± SE, and p < .05 was considered significant.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
DISCUSSION
 ACKNOWLEDGMENTS
 REFERENCES
 
A significant decrease (p < .05) in the anti-EBNA IgG was found at L-10 as compared with baseline (Figure 1). Anti-EBNA antibodies further decreased (p < .01) after flight (R+0 and R+3) as compared with baseline values. Anti-VCA was significantly increased (p < .01) at all three time points (L-10, R+0, and R+3) as compared with baseline. No significant difference was found in anti-measles antibodies at any time point.



View larger version (20K):
[in this window]
[in a new window]
  		Fig. 1. Change in anti-VCA, anti-EBNA, and anti-measles virus IgG antibody titers before (AME and L-10) and after (R+0 and R+3) spaceflight. AME = annual medical exam (baseline). *p < .05; **p < .01.

 
The control group showed no significant change between baseline and day 15 samples in either the log2 VCA IgG antibody titers (9.2 ± 0.3 vs. 9.6 ± 0.2, p = .2) or the log2 EBNA IgG antibody titers (4.3 ± 0.4 vs. 4.4 ± 0.4, p = .8). In addition, no change was found in the antibody titers to the nonlatent measles virus (6.0 ± 0.5 baseline vs. 5.6 ± 0.4 at day 15, p = .6).

The postflight changes in neuroendocrine hormones are shown in Figure 2. No significant change was found for plasma cortisol (p = .4) or urinary epinephrine (p = .058). However, significant increases were found at landing for urinary cortisol (p < .01) and norepinephrine (p < .05). In our previous study (16), 11 of these subjects had serological evidence of EBV reactivation (defined as EBV-VCA/early antigen titers of 5120/160 or an eight-fold increase in IgG antibody titers). The stress hormone data were therefore grouped between those with and without evidence of EBV reactivation. No difference was found in the average percentage of change in plasma cortisol between the two groups (data not shown). No statistical difference (p = .1) was found in urinary cortisol for astronauts with EBV reactivation as compared with those without EBV reactivation (93% and 23%; Figure 3). Epinephrine and norepinephrine were increased in the EBV-reactivating group (220% and 100% vs. -1% and 1% in the nonreactivating group, respectively). These differences were statistically significant at p < .05 and p < .025, respectively. Interestingly, 9 of 11 astronauts in the EBV-reactivating group had a greater than 70% increase in epinephrine, as compared with 3 of 17 astronauts in the nonreactivating group (p = .006). In addition, the number of astronauts in the EBV-reactivating group with a 50% or more increase in norepinephrine was greater than the number in the nonreactivating group (10 of 11 vs. 2 of 17, respectively; p = .001).



View larger version (28K):
[in this window]
[in a new window]
  		Fig. 2. Changes in plasma cortisol (PCort; µg/dl) and urinary cortisol (UCort), epinephrine (UEpi), and norepinephrine (UNor; all µg/24 h) at landing (R+0) as compared with preflight (L-10) levels. *p < .05.

 


View larger version (29K):
[in this window]
[in a new window]
  		Fig. 3. Postflight changes in stress hormones in astronauts with or without evidence of EBV reactivation after spaceflight. Cortisol = urinary cortisol; EPI = urinary epinephrine; NE = urinary norepinephrine. *p < .05; **p < .025.

 
Table 1 shows the characteristics of the astronauts with and without evidence of EBV reactivation. The ages for both groups were not significantly different. No difference was detected between the two groups when accounting for pilot/commander positions vs. mission/payload specialist positions (p = 1.0). Furthermore, no significant difference was found between first-time flyers and those with previous Shuttle mission experience (p = .3).


View this table:
[in this window]
[in a new window]
  		Table 1. Subject Characteristics
 

   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
ACKNOWLEDGMENTS
 REFERENCES
 
In the current study, further evidence was obtained consistent with stress-induced changes in immune function before flight whereby anti-EBNA antibodies were decreased at L-10 as compared with baseline values. Moreover, anti-EBNA antibodies continued to decrease after spaceflight. These results are similar to those from psychological stress studies, in which examination stress resulted in decreased EBV-specific cytotoxic T-cell function and increased antibodies to latent herpesviruses (reviewed in Ref. 25). Although a limitation in this study was the lack of a baseline (ie, annual medical exam) sample for the control group, no change was observed in antibodies to the nonlatent measles virus for either group. Moreover, the increase in anti-VCA antibodies along with the lack of change in measles virus antibodies indicated reactivation of latent EBV in astronauts, and this occurred presumably as a result of stress. Indeed, the physical and mental rigors of training for a flight (ie, review of assigned flight tasks, public affair events, and family time) culminate in the few weeks just before the mission (communication from crew members). These results, along with previous findings (7, 16), support the hypothesis that cellular immunity is already decreased before spaceflight.

No increase in plasma cortisol was observed after spaceflight in the present study. One plausible explanation for this finding is variability due to the circadian rhythm of cortisol. The landing day blood samples were taken in the early afternoon, whereas the preflight samples were taken in the early morning. As such, it would be expected that plasma cortisol would be unchanged or decreased. However, a significant increase in cortisol was found as reflected by the 24-hour urinary values. This increase is thought to reflect an acute stress response to G-force acceleration encountered during atmospheric reentry (7, 18). In support of this notion, significant increases in plasma cortisol were found in blood samples taken with 30 minutes of 3-G centrifugation (26). Therefore, the lack of correlation between plasma and urinary cortisol values may reflect the difference in blood sampling vs. stimulus time ({approx}4 hours), and this interpretation is supported by the short half-life (~90 minutes) of circulating cortisol (27). Considering the multiple variables involved in spaceflight experiments (ie, G forces, time of postflight blood draws, length of missions, etc.), measurement of cortisol in urine samples is critical to accurately assess its release. Thus, 24-hour urinary cortisol levels may be a better overall indicator of stress than plasma levels.

Greater increases in catecholamines were found in the EBV-reactivating group as compared with the nonreactivating group. However, no significant differences were found in cortisol between the two groups. Glucocorticoids, but not catecholamines, have been shown to directly modulate reactivation of EBV (24), so EBV reactivation in these subjects cannot be attributed solely as a result of elevated cortisol. Interestingly, catecholamines have been shown to play an important role in modulating virus-specific CD8+ T-cell function. Dobbs et al. (28) found that blockage of type II glucocorticoid receptors only partially restored virus-specific T-cell cytotoxicity in a murine model of herpes simplex infection; the addition of a ß-adrenergic antagonist was required to fully restore this activity. Perhaps the increased catecholamine levels in the EBV-reactivating group significantly suppressed virus-specific T-cell activity in these individuals, resulting in enhanced viral reactivation and replication. Support for this hypothesis comes from the postflight decreases in anti-EBNA antibody titers, although limited plasma sample volumes resulted in antibody titer data for only 6 of 11 astronauts in the EBV-reactivating group, which precluded direct comparison of anti-EBNA values between the two groups. Thus, EBV reactivation in these astronauts may have resulted from both direct (ie, stress hormones) and indirect (ie, decreased immune function) mechanisms.

A common supposition is that first-time flyers and nonmilitary astronauts may be more susceptible to stress and other physiological changes associated with spaceflight. Buckey et al. (29) found that eight of nine presyncopal astronauts (89%) were either payload or mission specialists, and subsequent studies have found similar results when astronauts were grouped according to aviation experience (30). In contrast, we found no correlation of latent EBV reactivation between commanders or pilots and mission or payload specialists. In addition, no correlation was found between first-time flyers and those with previous spaceflight experience. These results indicate that EBV reactivation is not higher in any specific group or related to flight experience. However, it will be important to confirm these observations with a larger number of astronauts in future studies.

In summary, it will be important to determine the magnitude of "immune suppression" and herpesvirus reactivation in astronauts during spaceflight, which may be due in part to confinement, sleep deprivation, and acute changes in gravitational forces. In addition, immunological "recovery," which may vary with the time spent in space, will be important to investigate given the increased frequency of acute respiratory and other viral illnesses that have occurred after long-duration spaceflight (3). Although the clinical significance of these findings remains to be determined, recurrent herpesvirus infections (which are not mitigated by current measures limiting preflight access to astronauts) may be an important health concern on long-term spaceflights. Our future studies will include direct measurement of virus-specific T-cells (ie, tetramers and ELISPOT) in conjunction with measurements of stress and latent herpesvirus reactivation to address these critical questions.


   ACKNOWLEDGMENTS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 ACKNOWLEDGMENTS
REFERENCES
 
We thank the astronaut subjects and mission planners involved in this study. We are grateful to Wyle Laboratories, Houston, TX, for their support. This work was supported in part by the National Aeronautics and Space Administration (Grant NGT-51666 to R.P.S. and Grant 106-20 to D.L.P.); the Sealy Center on Aging, University of Texas Medical Branch; and the Space Industrial Fellowship–Houston Advanced Research Center.

Received for publication September 12, 2000.


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 ACKNOWLEDGMENTS
 REFERENCES
 

  1. Taylor GR, Neale LS, Dardano JR. Immunologic analysis of U.S. Space Shuttle crew members. Aviat Space Environ Med 1986; 57: 213–7.[Medline]
  2. Taylor GR, Janney RP. In vivo testing confirms a blunting of the human cell-mediated immune mechanism during spaceflight. J Leukoc Biol 1992; 51: 129–32.[Abstract]
  3. Konstantinova IV. Immune system.In: Leach Huntoon CS, Antipov VV, Grigoriev AI, editors. Humans in spaceflight. Vol 3,book 1. Reston (VA): American Institute of Aeronautics and Astronautics, Inc; 1996.p. 117–33.
  4. Meehan RT, Whitson P, Sams CF. The role of psychoneuroendocrine factors on spaceflight-induced immunological alterations. J Leukoc Biol 1993; 54: 236–44.[Abstract]
  5. Gmunder FK, Konstantinova I, Cogoli A, Lesnyak A, Bogomolov W, Grachov W. Cellular immunity in cosmonauts during long duration spaceflight on board the orbital MIR station. Aviat Space Environ Med 1994; 65: 419–23.[Medline]
  6. Taylor GR, Konstantinova I, Sonnenfeld G, Jennings R. Changes in the immune system during and after spaceflight. Adv Space Biol Med 1997; 6: 1–32.[Medline]
  7. Stowe RP, Sams CF, Mehta SK, Kaur I, Jones ML, Feeback DL, Pierson DL. Leukocyte subsets and neutrophil function after short-term spaceflight. J Leukoc Biol 1999; 65: 179–86.[Abstract]
  8. Glaser R, Kiecolt-Glaser JK, Bonneau RH, Malarkey W, Kennedy S, Hughes J. Stress-induced modulation of the immune response to recombinant hepatitis B vaccine. Psychosom Med 1992; 54: 22–9.[Abstract/Free Full Text]
  9. Sheridan JF, Feng N, Bonneau RH, Allen CM, Huneycutt BS, Glaser R. Restraint stress differentially affects anti-viral cellular and humoral responses in mice. J Neuroimmunol 1991; 31: 245–55.[Medline]
  10. Jones J, Katz BZ. Epstein-Barr virus infections in normal and immunocompromised patients.In: Glaser R, Jones JF, editors. Herpesvirus infections. New York: Marcel Dekker; 1994.p. 187–226.
  11. Okano M, Thiele GM, Davis JR, Grierson HL, Purtilo DT. Epstein-Barr virus and human disease: recent advances in diagnosis. Clin Microbiol Rev 1988; 1: 300–12.[Abstract/Free Full Text]
  12. Riddler SA, Breinig MC, McKnight JLC. Increased levels of circulating Epstein-Barr virus (EBV)–infected lymphocytes and decreased EBV nuclear antigen antibody responses are associated with the development of posttransplant lymphoproliferative disease in solid-organ transplant recipients. Blood 1994; 84: 972–84.[Abstract/Free Full Text]
  13. Ho M, Miller G, Atchinson RW, Breinig MK, Dummer JS, Andiman W, Starzl TE, Eastman R, Griffith BP, Hardesty RL, Bahnson HT, Hakala TR, Rosenthal JT. Epstein-Barr virus infections and DNA hybridization studies in post-transplantation lymphoma and lymphoproliferative lesions: the role of primary infection. J Infect Dis 1985; 152: 876–86.[Medline]
  14. Preiksaitis JK, Diaz-Mitoma F, Mirzayans F, Roberts S, Tyrrell DLJ. Quantitative oropharyngeal Epstein-Barr virus shedding in renal and cardiac transplant recipients: relationship to immunosuppressive therapy, serologic responses, and the risk of posttransplant lymphoproliferative disorder. J Infect Dis 1992; 166: 986–94.[Medline]
  15. Kusunoki Y, Huang H, Fukuda Y, Ozaki K, Saito M, Hirai Y, Akiyama M. A positive correlation between the precursor frequency of cytotoxic lymphocytes to autologous Epstein-Barr virus-transformed B cells and antibody titer levels against Epstein-Barr virus–associated nuclear antigen in healthy seropositive individuals. Microbiol Immunol 1993; 37: 461–9.[Medline]
  16. Stowe RP, Pierson DL, Feeback DL, Barrett ADT. Stress-induced reactivation of Epstein-Barr Virus in astronauts. Neuroimmunomodulation 2000; 8: 51–8.[Medline]
  17. Stein TP, Schluter MD. Excretion of IL-6 by astronauts during spaceflight. Am J Physiol 1994; 266: E448–52.[Abstract/Free Full Text]
  18. Leach CS, Alfrey CP, Suki WN, Leonard JI, Rambaut PC, Inners DL, Smith SM, Lane HW, Kraus JM. Regulation of body fluid compartments during short-term spaceflight. J Appl Physiol 1996; 81: 105–16.[Abstract/Free Full Text]
  19. Blotta MH, DeKruyff RH, Umetsu DT. Corticosteroids inhibit IL-12 production in human monocytes and enhance their capacity to induce IL-4 synthesis in CD4+ lymphocytes. J Immunol 1997; 158: 5589–95.[Abstract]
  20. DeKruyff RH, Fang Y, Umetsu DT. Corticosteroids enhance the capacity of macrophages to induce Th2 cytokine synthesis in CD4+ lymphocytes by inhibiting IL-12 production. J Immunol 1998; 160: 2231–7.[Abstract/Free Full Text]
  21. Elenkov IJ, Papanicolaou DA, Wilder RA, Chrousos GP. Modulatory effects of glucocorticoids and catecholamines on human interleukin-12 and interleukin-10 production: clinical implications. Proc Am Assoc Physicians 1996; 108: 374–81.
  22. Kupfer SR, Summers WC. Identification of a glucocorticoid-responsive element in Epstein-Barr virus. J Virol 1990; 64: 1984–90.[Abstract/Free Full Text]
  23. Schuster C, Chasserot-Golaz S, Beck G. Activation of Epstein-Barr virus promoters by a growth-factor and a glucocorticoid. FEBS Lett 1991; 284: 82–6.[Medline]
  24. Glaser R, Kutz LA, MacCallum RC, Malarkey WB. Hormonal modulation of Epstein-Barr virus replication. Neuroendocrinology 1995; 62: 356–61.[Medline]
  25. Rozlog LA, Kiecolt-Glaser JK, Marucha PT, Sheridan JF, Glaser R. Stress and immunity: implications for viral disease and wound healing. J Periodontol 1999; 70: 786–92.[Medline]
  26. Vernikos J. Metabolic and endocrine changes.In: Sandler H, Vernikos J, editors. Inactivity: physiological effects. New York: Academic Press; 1986.p. 99–121.
  27. Kehrl JH, Fauci AS. The clinical use of glucocorticoids. Ann Allergy 1983; 50: 2–8.[Medline]
  28. Dobbs CM, Vasquez M, Glaser R, Sheridan JF. Mechanisms of stress-induced modulation of viral pathogenesis and immunity. J Neuroimmunol 1993; 48: 151–60.[Medline]
  29. Buckey JC, Lane LD, Levine BD, Watenpaugh DE, Wright SJ, Moore WE, Gaffney FA, Blomqvist CG. Orthostatic intolerance after spaceflight. J Appl Physiol 1996; 81: 7–18.[Abstract/Free Full Text]
  30. Lee SM, Moore AD, Fritsch-Yelle JM, Greenisen MC, Schneider SM. Inflight exercise affects stand test responses after spaceflight. Med Sci Sports Exerc 1999; 31: 1755–62.[Medline]



This article has been cited by other articles:


Home page
 CVIHome page
I. Kaur, E. R. Simons, A. S. Kapadia, C. M. Ott, and D. L. Pierson
Effect of Spaceflight on Ability of Monocytes To Respond to Endotoxins of Gram-Negative Bacteria
Clin. Vaccine Immunol., October 1, 2008; 15(10): 1523 - 1528.
[Abstract] [Full Text] [PDF]

Home page
 J. Appl. Physiol.Home page
R. Boxio, C. Dournon, and J.-P. Frippiat
Effects of a long-term spaceflight on immunoglobulin heavy chains of the urodele amphibian Pleurodeles waltl
J Appl Physiol, March 1, 2005; 98(3): 905 - 910.
[Abstract] [Full Text] [PDF]

Home page
 J. Appl. Physiol.Home page
Z. Li, C. A. Rivera, A. R. Burns, and C. W. Smith
Hindlimb unloading depresses corneal epithelial wound healing in mice
J Appl Physiol, August 1, 2004; 97(2): 641 - 647.
[Abstract] [Full Text] [PDF]

Home page
 Mult SclerHome page
R. D Simmons, A.-L. Ponsonby, I. A. van der Mei, and P. Sheridan
What affects your MS? Responses to an anonymous, Internet-based epidemiological survey
Multiple Sclerosis, April 1, 2004; 10(2): 202 - 211.
[Abstract] [PDF]

Home page
 Psychosom. Med.Home page
M. G. Ziegler and J. V. Meck
Physical and Psychological Challenges of Space Travel: An Overview
Psychosom Med, November 1, 2001; 63(6): 859 - 861.
[Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Figures Only
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Stowe, R. P.
Right arrow Articles by Barrett, A. D. T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Stowe, R. P.
Right arrow Articles by Barrett, A. D. T.
Related Collections
Right arrow Immunology
Right arrow Infectious Disease

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS