10
Immunology

Introduction

Spaceflight produces marked effects on several parameters of immune responses. Neither the biological or biomedical significance nor the mechanism(s) of induction of these changes have yet been established.

Multiple factors could be involved in the effects of spaceflight on immune responses. In spaceflight as on Earth, the immune system interacts dynamically with other body systems. Factors that must be considered during spaceflight include changes induced by microgravity; changes induced in the neuroendocrine stress hormone system and other stress responses; and changes induced by exposure to radiation, by alterations in nutritional intake, by alterations in levels of 1,25-dihydroxyvitamin D3 (i.e., changes in calcium), by acceleration and deceleration forces, and by possible alterations in prolactin and growth hormone levels. 1 2 3 These factors may act independently or combine with effects of exposure to microgravity to produce additive or synergistic effects on the immune system. For example, changes in diet and workload during spaceflight could trigger hormonal responses that in turn affect immune responses. The interaction of the immune response with the hypothalamic-pituitary-adrenal (HPA) axis could also play a major role. The discipline of psychoneuroimmunology has recently been established to facilitate the study of these interactions.4 It appears that there is major interaction between these two systems, and factors such as stress can have a great impact on immune responses and resistance to infection. These interactions could play a major role as one potential mechanism for the effects of spaceflight on immune responses. Additional and as yet unknown factors could also play some role.

A variety of observations made during and after spaceflights have generated an interest in the effects of spaceflight on immune responses. Many of the early studies reporting possible infections may actually have observed "space motion sickness" and headward fluid shifts that produced symptoms that at that time were indistinguishable from those of the common cold and influenza.5 Astronauts who



The National Academies | 500 Fifth St. N.W. | Washington, D.C. 20001
Copyright © National Academy of Sciences. All rights reserved.
Terms of Use and Privacy Statement



Below are the first 10 and last 10 pages of uncorrected machine-read text (when available) of this chapter, followed by the top 30 algorithmically extracted key phrases from the chapter as a whole.
Intended to provide our own search engines and external engines with highly rich, chapter-representative searchable text on the opening pages of each chapter. Because it is UNCORRECTED material, please consider the following text as a useful but insufficient proxy for the authoritative book pages.

Do not use for reproduction, copying, pasting, or reading; exclusively for search engines.

OCR for page 156
--> 10 Immunology Introduction Spaceflight produces marked effects on several parameters of immune responses. Neither the biological or biomedical significance nor the mechanism(s) of induction of these changes have yet been established. Multiple factors could be involved in the effects of spaceflight on immune responses. In spaceflight as on Earth, the immune system interacts dynamically with other body systems. Factors that must be considered during spaceflight include changes induced by microgravity; changes induced in the neuroendocrine stress hormone system and other stress responses; and changes induced by exposure to radiation, by alterations in nutritional intake, by alterations in levels of 1,25-dihydroxyvitamin D3 (i.e., changes in calcium), by acceleration and deceleration forces, and by possible alterations in prolactin and growth hormone levels. 1 2 3 These factors may act independently or combine with effects of exposure to microgravity to produce additive or synergistic effects on the immune system. For example, changes in diet and workload during spaceflight could trigger hormonal responses that in turn affect immune responses. The interaction of the immune response with the hypothalamic-pituitary-adrenal (HPA) axis could also play a major role. The discipline of psychoneuroimmunology has recently been established to facilitate the study of these interactions.4 It appears that there is major interaction between these two systems, and factors such as stress can have a great impact on immune responses and resistance to infection. These interactions could play a major role as one potential mechanism for the effects of spaceflight on immune responses. Additional and as yet unknown factors could also play some role. A variety of observations made during and after spaceflights have generated an interest in the effects of spaceflight on immune responses. Many of the early studies reporting possible infections may actually have observed "space motion sickness" and headward fluid shifts that produced symptoms that at that time were indistinguishable from those of the common cold and influenza.5 Astronauts who

OCR for page 156
--> were isolated before flight in Apollo missions had decreased problems with upper respiratory tract infections compared to those not isolated. 6 7 During the Apollo 13 mission, one astronaut developed a urinary tract infection from Pseudomonas aeruginosa.8 9 One Mir cosmonaut was removed from the space station because of possible but unconfirmed upper respiratory tract infections (I. Konstantinova, personal communication, 1992).10 These results are evidence of limited problems with infectious diseases during spaceflight.11 To date, there has been no evidence of extensive problems with infections during and after spaceflight. However, as plans for very long term missions and colonies in space develop, the potential for problems with infectious diseases increases and should be explored. In addition, the role of microgravity in spaceflight-induced alterations of in vivo immune responses has not yet been established. Spaceflight Experiments Animal Studies Animal studies have focused on cell-mediated immunity and have attempted to evaluate the greatest possible number of immunological parameters affected by spaceflight.12 13 Studies on antibody responses, mechanistic studies, and studies to determine the biological and biomedical significance of spaceflight-induced alterations in immunological parameters have been few in number and limited in scope, owing primarily to technical difficulties in carrying out experiments and not to lack of interest or potential effects. Most spaceflight studies conducted with animals have involved specimens shared by multiple research groups in different disciplines. Experiments have had to be designed so that they would not interfere with or compromise other experiments. Therefore, studies involving resistance to infections, sensitization to an antigen, and determination of antibody levels have not been carried out. Access to and experimentation on animals during flight in current spacecraft is also difficult and has been conducted in only a limited fashion. Most studies have been carried out immediately upon return of the animals to Earth. Reentry acceleration and other forces could have affected results obtained after landing.14 15 The principal experimental mammalian animal for spaceflight studies has been the rat. Housing suitable for spaceflight has been developed for rats. In addition, because of its larger size, the rat has been most useful for studies requiring sharing of tissues among different experimental groups. Multiple modifications currently under development will be required before housing for spaceflight will be available for use with mice. However, use of the mouse in spaceflight studies has several benefits, including (1) the potential for using more animals in one study, (2) the availability of many immunological reagents that are specific for mice and unavailable for rats, and (3) the ability to use genetically unique strains of mice (including "knockout" and transgenic mice) for study. A limited number of studies have been carried out with rhesus monkeys.16 17 Experiments have been carried out using both Russian and U.S. spacecraft. Although housing, in-flight environmental conditions, duration and apogee of flight, and landing conditions have differed, the results have generally been consistent.18 19 20 21 22 23 24 25 26 27 28 29 30 All flights carrying experimental animals have been of relatively short duration, usually from 1 to 2 weeks. Almost all experiments, except where noted, have been carried out immediately after return to Earth (usually within 2 to 4 hours, but sometimes as late as 24 hours after return). Early studies indicated involution of the thymus after spaceflight. 31 Alterations in thymus and other tissue were later confirmed but shown to possibly be transient in nature.32 33 Although early experiments carried out in the Russian Cosmos biosatellite to determine the effects

OCR for page 156
--> of spaceflight on rat leukocyte blastogenesis showed no effects of spaceflight,34 later studies found compartmentalization of the effects of spaceflight on blastogenesis. Leukocytes obtained from lymph nodes were affected differently from cells obtained from systemic tissue. 35 36 The majority of studies have involved acquired immunity (specific immunity to pathogens and tumors requiring previous exposure to the pathogen or tumor). An experiment with rats flown on the Space Shuttle mission SL-3 studied production of cytokines (soluble mediators such as interleukins and interferons that carry messages between cells of the immune response) after landing.37 Spleens were removed from the rats within a few hours after landing and challenged with mitogen to induce cytokine production. Interferon-γ production was greatly reduced; however, interleukin-3 measurements made of the same culture's supernatant fluids showed no decrease in interleukin-3 production. Later work showed decreases in the production of other cytokines, including interleukin-2, only at certain times after spaceflight. 38 39 Production of other cytokines such as interleukin-3 and interleukin-6 also increased after spaceflight.40 However, there was compartmentalization of these responses; production of interleukin-6 by spleen cells was unaffected, but production of interleukin-6 by thymus cells increased. Compartmentalization indicates that there is no overall blunting of the immune response after spaceflight, but selective effects instead. 41 Although studies of the effects of spaceflight on cytokine production have been carried out, there has never been an attempt to establish whether or not spaceflight induces changes in Th1 and Th2 cytokine production profiles of helper T lymphocytes. A Th1 cytokine production profile indicates a prevalence toward development of cell-mediated immune reactions, whereas a Th2 cytokine production profile shows a prevalence toward development of antibody-mediated immunity. Shifts between Th1 and Th2 profiles of cytokine production could indicate spaceflight-induced regulatory changes in immune responses and could be of great significance. Some studies have been conducted on the effects of spaceflight on innate immunity (nonspecific immunity always present). Initial studies on cells from rats flown on the Russian Cosmos biosatellite showed a decrease in the ability of spleen natural killer cells to kill target tumor cells compared with controls, but later studies showed that this was selective; the ability of natural killer cells from animals flown in space to kill different target tumor cells was unaffected. 42 These measurements were made in cells from animals euthanized immediately after flight. In later experiments, rats were euthanized in-flight aboard the Space Shuttle mission SLS-2.43 This was the first in-flight animal study, and the animals were euthanized 1 day before landing. Spleens were removed and refrigerated, and the assay was carried out after landing. In this case, the ability of spleen cells from the rats euthanized in space to kill both types of tumor target cells was inhibited compared with that of spleen cells from controls euthanized on Earth and maintained at 4°C for the same length of time as the in-flight samples. When spleen cells from animals flown aboard SLS-2 but euthanized immediately upon return to Earth were tested, only the ability to kill 1 type of target cells was affected,44 repeating the results of previous studies. These important data indicate that in-flight sampling is extremely important, as some immunological changes occurring during flight could reverse very rapidly after a return to Earth from space. Experiments have also centered on colony stimulating factor responsiveness and leukocyte subset distribution. The response to colony stimulating factors of bone marrow cells from rats flown on several Russian Cosmos biosatellite missions has been examined.45 46 The response of cells from rats flown in space to both granulocyte-macrophage colony stimulating factor and macrophage colony stimulating factor was greatly reduced after spaceflight, compared with the response of cells from control animals housed in normal caging or in caging designed to simulate conditions in the space capsule.47 48 Some alterations in leukocyte subset distribution were also noted after spaceflight of rats on the Cosmos capsule and the space shuttle, most notably an increase in the level of CD4+ helper T cells.49 50 51 52

OCR for page 156
--> A control experiment was carried out using centrifugation of rats on Earth in housing conditions similar to those used in the Cosmos biosatellite flight studies to determine if hypergravity could affect immune parameters. Hypergravity had no effect on any of the immune parameters shown to be affected during the Cosmos biosatellite flights. 53 Results from one flight experiment using rhesus monkeys have been generally consistent with those observed using rats; in rhesus monkeys flown in a Russian Cosmos biosatellite mission, interleukin-1 levels, interleukin-2 receptor levels, and bone marrow cell responses to granulocyte-macrophage colony stimulating factor decreased.54 Although this evidence shows that immunological parameters are affected by spaceflight, no evidence to date indicates that these changes are of biological or medical significance. The use of animal models could help to resolve this uncertainty and could influence future considerations as to whether spaceflight-induced changes in immune parameters are an important issue for the health and safety of space travelers. This issue should be given the highest priority. One reason that this issue has not been addressed before is that animals have had to be shared among investigators in multiple disciplines, and so carrying out functional immunological studies could affect the results of other investigators in other disciplines. It is hoped that research in the International Space Station era will allow assignment of specific animals for these important immunological studies. Mice would be the species of choice for the studies because of the plethora of immunological reagents available. Functional immunological studies could also be performed in the rat, the rodent species used most frequently in previous spaceflight studies. If studies using monkeys are carried out again, immunological experiments could be included using this species. Recommendations The biological and biomedical significance of spaceflight-induced changes in immune responses should be investigated in both short- and long-term studies, preferably in mice or, if necessary, in rats. The types of animal studies that should be carried out, listed in priority order, include the following: Resistance to infection. Studies of resistance to infection might create some difficulty if carried out entirely in the space station environment, because of the difficulty in bringing potential pathogens into that environment. Therefore, studies of infection should not be carried out on board the space station or the space shuttle but should be performed on animals flown in space immediately upon their return to Earth. This would model the period immediately after return to Earth when crews leave closed environments, which could be the time of crew members' greatest risk from infection. All other animal studies should be carried out both on the space station and upon return to Earth. Animals exposed to spaceflight conditions or suspension modeling for short- or long-term periods should be infected with viruses (e.g., influenza and herpes viruses) or bacteria (e.g., Salmonella typhimurium) and spaceflight-induced changes in resistance to infection determined. These would test the relevance of spaceflight effects on both antibody and cell-mediated immunity. Acquired immune responses Studies of antigen sensitization and resistance to infections should be carried out to determine if spaceflight affects the ability to mount a new immune response and resistance to infection. Sensitization studies could be carried out in-flight using innocuous sensitizing antigens such as keyhole limpet hemocyanin.

OCR for page 156
--> Humoral immune responses should be tested directly after immunization and challenge by determination of antibody specificity and type. Th1 and Th2 cytokine profiles should be established, not only in nonimmune animals but also following specific immune challenge. Cell-mediated immunity should be tested with both delayed-type hypersensitivity responses to contact-sensitivity agents, and generation of cytotoxic T lymphocyte activity. Interactions with the HPA-axis and other body systems. When measurements are taken for immune responses, simultaneous determination of stress-related mediators (including stress hormones, catecholamines, and neuropeptide Y) should be carried out. Measurements of blood pressure, heart rate, orthostatic intolerance, and other appropriate variables/parameters should also be collated and made available to allow determination of interactions of the immune system with other body systems, including the musculoskeletal system. Human Studies Few studies have been carried out to determine the effects of spaceflight on immune responses of humans. Human experimentation has been restricted because of necessary limited access to crew members. However, it has been possible to study the effects of long-term spaceflights of several months to greater than 1 year.55 Several alterations in immunological parameters have been observed in crew members after short-term space shuttle flights. These studies were carried out after landing, and so the relative roles played by microgravity, psychological stress, and landing stresses in inducing the alterations cannot be differentiated. The results presented here are a consensus of data from most flight studies, although contradictory data do exist. The alterations reported include decreases in lymphocyte number, decreases in leukocyte blastogenesis, increases in leukocyte number, alterations in the relative percentage of B and T lymphocytes, decreases in monocytes, increases in helper T lymphocytes, decreases in cytotoxic T lymphocytes, and an increase in the ratio of CD4+/CD8+ lymphocytes.56 57 58 59 These alternatives may be associated with certain neuroendocrine system changes, particularly in catecholamines such as epinephrine and norepinephrine.60 Again, it must be noted that there are individual flights where there have been no changes or changes with shifts in the opposite direction from those reported in the summary above. Conditions, including flight duration, have varied for every flight. This variability makes it difficult to obtain a standard effect of spaceflight on every immunological parameter. Regardless of the individual flight-specific differences in results, it is clear from the data to date that spaceflight can alter immunological parameters. Changes observed in cells obtained from cosmonauts immediately after Russian short-term flights include decreases in natural killer cell activity and decreases in production of interferon-α/β.61 62 63 Interestingly, the decreased interferon-α/β production was from the same mission and the same cosmonauts whose peripheral blood leukocytes were placed in culture and challenged with an interferon inducer in the in vitro space experiment of Tálas et al., in which interferon-α/β production was markedly enhanced.64 These results reiterate the point that in vitro spaceflight results may not be representative of the in vivo situation, because cells in culture are not in their normal environment involving interactions with other body systems. When testing was carried out on samples from cosmonauts immediately upon their return to Earth after long-duration spaceflight, the most prominent effects were alterations in natural killer cell activity, alterations in leukocyte blastogenesis, and alterations in interleukin-2 production.65 66 The same studies also

OCR for page 156
--> reported increases in the level of serum immunoglobulins, particularly total serum IgA and IgM. The adaptability of the human immune system to long-term spaceflight conditions has yet to be established. Some recent attempts have been made to address the issue of sampling of spaceflight effects on the immune response of humans in midflight. 67 68 These are significant studies, as they allow for differentiation between spaceflight effects and landing stress effects on immune responses. Additional studies of this nature are needed. These results were originally reported with data obtained from astronauts during relatively short-term space shuttle flight69 but have been extended to longer-term Mir space station experiments.70 These experiments involved delayed hypersensitivity skin testing to common recall antigens and did show an effect of spaceflight. There was a marked decrease in the skin-test response to these antigens when the crews were tested during spaceflight. Recommendations Immunological measurements and testing of humans should be carried out to look at parameters with potential functional consequences. Additional human immunological studies and development of potential countermeasures should be conducted only if the animal infection studies and the initial human functional studies show that spaceflight-induced changes in immune parameters are of biological and biomedical importance. The following studies, listed in order of priority, should be carried out: Acquired immunity Delayed-type hypersensitivity responses should be tested in-flight and postflight to expand this database. Influenza vaccine responses should be monitored in spaceflight and after return to Earth to test both T helper cell function and antibody production. Antibody responses to latent viral epitopes such as oral herpes virus or Epstein-Barr virus should be determined. If the animal infection studies and the above-mentioned human functional immunity studies show biologically and biomedically important results, then both ground-based and in-flight studies of Th1 (cell-mediated) cytokines (e.g., interleukin-2, interferon-γ, interleukin-12) and Th2 (humoral) cytokines (e.g., interleukin-4, interleukin-10) should be conducted. Each subject should be used as his or her own control, to ensure that individual variation is taken into consideration for each experiment and to allow all subjects to be followed longitudinally over time. Innate immunity. Natural killer cell numbers and activity, as well as neutrophil function (oxygen burst activity) using peripheral blood samples should be measured. Epidemiological studies. To assess potential risk from infection (and in particular, tumors), complete, longitudinal, and comprehensive records should be kept for all space travelers and should be made available for epidemiological studies and risk assessment. Interactions with the HPA-axis and other body systems. In humans exposed to ground-based modeling and to spaceflight, when measurements are taken for immune responses, simultaneous determination of stress-related mediators (including stress hormones, catecholamines, and neuropeptide Y) should be carried out. Measurements of blood pressure, heart rate, orthostatic intolerance, and other appropriate parameters should also be collated and made available to allow determination of interactions of the immune system with other body systems, including the musculoskeletal system.

OCR for page 156
--> Cell Culture Studies In cell culture studies of the immune system, cells are isolated from their normal interactions with other body systems such as the neuroendocrine, cardiovascular, and musculoskeletal systems. Results of these studies are not necessarily representative of events occurring in vivo. All space-based studies to date of cells in culture have been limited by technical limitations of the equipment available, leading to limitations on the design of experiments (see Chapter 2). Early studies indicated that mitogen-mediated blastogenesis of human peripheral blood leukocytes grown in culture during spaceflights was severely inhibited.71 72 73 74 This was attributed to a possible direct effect of microgravity on lymphocytes. However, other mechanisms could possibly be involved. For example, blastogenesis of lymphocytes requires the assistance of macrophages as accessory cells. Changes in fluid convection due to microgravity could have prevented necessary interactions between lymphocytes and macrophages that could have led to inhibited blastogenesis after spaceflight.75 76 There have also been some reports of hypergravity enhancing in vitro leukocyte blastogenesis, although the mechanism remains open to debate.77 Changes in T cell and macrophage function have also been reported.78 79 80 81 Killing of target cells by tumor necrosis factor-α was also inhibited in spaceflight by a mechanism involving protein kinase C; however, no effect on production of superoxide was noted.82 83 Studies have shown enhanced interferon-, interleukin-1, interleukin-2, and tumor necrosis factor-α production from cultures of lymphoid cells flown in space.84 85 86 87 88 89 90 All of these experiments require additional studies to confirm results. Recommendation Although cell culture results may not exactly mirror events in vivo, they are potentially useful for exploration of mechanisms. These studies should be carried out after confirmation of the biological and biomedical importance of the effects of spaceflight on the immune systems. Hypothesis-driven tissue culture studies of immune cells in spaceflight should be carried out only after there is proof of biological significance and with availability of reliable tissue culture hardware, including in-flight centrifuge controls. Ground-based Models of the Effects of Spaceflight on Immune Responses Ground-based models of some of the effects of spaceflight on immune responses have become a major step in the design of spaceflight experiments. Because opportunities to carry out flight experiments are relatively rare and very expensive, modeling is useful in planning for flight experiments. Since it is impossible to faithfully model microgravity on Earth, all models have deficiencies and strengths that must be taken into consideration in evaluating results. Models that have been used include hindlimb unloading in rodents,91 92 93 chronic bed rest in humans,94 95 96 and rotation of cells in a clinostat.97 Hindlimb unloading of rodents has been used to simulate some aspects of the effects of microgravity on immune responses. 98 Two different varieties of the model have been used: suspension by the tail and harness suspension.99 There are benefits and drawbacks to both varieties of the model; however, studies with both involving immune responses have shown similar results to date.100 101 102 103 104 105 Suspension of rats and mice with no load bearing on the hindlimbs and with head-down tilt (usually 15° to 20°) leads to bone and muscle disuse and a fluid shift to the head.

OCR for page 156
--> Although this model has many limitations because microgravity cannot be truly modeled on Earth, it is the best model available for rodent studies. One positive aspect of the use of hindlimb unloading with a head-down tilt is that rodents suspended without head-down tilt (i.e., no-head-down tilt rodents) can be used as a control for the stress of the model. Hindlimb unloading with a head-down tilt in rats has been show to yield changes in several dynamic immune parameters, but to have little to no effect on more static immune parameters.106 107 Immune parameters altered after hindlimb unloading with a head-down tilt of rodents have included interferon-α/β and -γ production, the response of bone marrow cells from suspended rats to exogenous colony stimulating factors, macrophage function, and interleukin production.108 109 110 111 There was no correlation between corticosterone levels and alterations in immune responses.112 The situation with neutrophil function is less clear; in mice, neutrophil function was inhibited after hindlimb unloading with a head-down tilt,113 whereas in rats, there was no effect on neutrophil function.114 There are several possible explanations for these differences, including differences in the type of hindlimb unloading used and the response of different species to hindlimb unloading. Immunological parameters such as leukocyte subset distribution were not affected by hindlimb unloading with a head-down tilt.115 116 117 The reason for differential effects on immune responses is not clear. Studies have shown that resistance to infection is altered by hindlimb unloading with a head-down tilt.118 Female mice normally resistant to infection with the [D] variant of encephalomyocarditis virus became susceptible to infection after 4 days of hindlimb unloading with a head-down tilt.119 The decreased resistance is correlated with the drop in interferon production seen after hindlimb unloading. In contrast, mice subjected to hindlimb unloading with a head-down tilt demonstrated enhanced immunological memory and resistance to infection with Listeria monocytogenes.120 121 These differences in resistance responses to bacteria and viruses may be related to differences in the effects of hindlimb unloading on the function of lymphocytes (for the virus) and macrophages (for the bacteria).122 123 124 Benefits can also be obtained using human models of spaceflight effects on immune responses. Several models have been used for immunological studies, including isolation, high altitude, and chronic bed rest. 125 126 127 128 129 130 131 Chronic bed rest is the most frequently used model and for humans is equivalent to hindlimb unloading with a head-down tilt in rodents. Bed rest eliminates load bearing on limbs and uses head-down tilt to model fluid shifts.132 Results of the various model studies cited above have demonstrated alterations in interferon and interleukin production. These include increases in interleukin-1 production (which could affect bone), decreases in interleukin-2 production, and changes in leukocyte subset distribution and in neutrophil and macrophage function. A clinostat is an apparatus that allows for rotation of cells so that the direction of the gravity vector is not constant.133 Its use for studies on cells important in the immune response, which do not have classical receptors for gravity, has been hotly debated. Nevertheless, rotation of cells in a clinostat has shown decreased T-lymphocyte activation134 and decreased leukocyte migration through type 1 collagen.135 Mechanisms that cause these changes in the clinostat may be different from those that could occur during spaceflight; however, the data obtained could prove useful in planning experiments to be carried out in space. References 1. Nicogossian, A.E., Huntoon, C.L., and Pool, S., eds. 1989. Space Physiology and Medicine, 2nd ed. Lea and Febiger, Philadelphia. 2. Churchill, S.E. 1997. Fundamentals of Space Life Sciences, Vols. 1 and 2. Krieger Publishing Co., Malabar, Fla. 3. Sonnenfeld, G., and Taylor, G.R. 1991. Effect of microgravity on the immune System. SAE Technical Paper Series No. 911515. Society of Automotive Engineers, Warrendale, Pa.

OCR for page 156
--> 4. Ader, R., Cohen, N., and Felten, D. 1995. Psychoneuroimmunology: Interactions between the nervous system and the immune system. Lancet 345: 99-103. 5. Taylor, G.R., Konstantinova, I.V., Sonnenfeld, G., and Jennings, R. 1997. Changes in the immune system during and after spaceflight. Adv. Space Biol. Med. 6: 1-32. 6. Taylor, G.R., Konstantinova, I.V., Sonnenfeld, G., and Jennings, R. 1997. Changes in the immune system during and after spaceflight. Adv. Space Biol. Med. 6: 1-32. 7. Taylor, G.R. 1974. Recovery of medically important microorganisms from Apollo astronauts. Aerosp. Med. 45: 824-828. 8. Taylor, G.R., Konstantinova, I.V., Sonnenfeld, G., and Jennings, R. 1997. Changes in the immune system during and after spaceflight. Adv. Space Biol. Med. 6: 1-32. 9. Taylor, G.R. 1974. Recovery of medically important microorganisms from Apollo astronauts. Aerosp. Med 45: 824-828. 10. Konstantinova, I.V., Rykova, M.P., Lesnyak, A.T., and Antropova, E.A. 1993. Immune changes during long duration missions. J. Leukocyte Biol. 54: 189-201. 11. Taylor, G.R., Konstantinova, I.V., Sonnenfeld, G., and Jennings, R. 1997. Changes in the immune system during and after spaceflight. Adv. Space Biol. Med. 6: 1-32. 12. Taylor, G.R., Konstantinova, I.V., Sonnenfeld, G., and Jennings, R. 1997. Changes in the immune system during and after spaceflight. Adv. Space Biol. Med. 6: 1-32. 13. Konstantinova, I.V., Rykova, M.P., Lesnyak, A.T., and Antropova, E.A. 1993. Immune changes during long duration missions. J. Leukocyte Biol. 54: 189-201. 14. Taylor, G.R., Konstantinova, I.V., Sonnenfeld, G., and Jennings, R. 1997. Changes in the immune system during and after spaceflight. Adv. Space Biol. Med. 6: 1-32. 15. Konstantinova, I.V., Rykova, M.P., Lesnyak, A.T., and Antropova, E.A. 1993. Immune changes during long duration missions. J. Leukocyte Biol. 54: 189-201 16. Taylor, G.R., Konstantinova, I.V., Sonnenfeld, G., and Jennings, R. 1997. Changes in the immune system during and after spaceflight. Adv. Space Biol. Med. 6: 1-32. 17. Konstantinova, I.V., Rykova, M.P., Lesnyak, A.T., and Antropova, E.A. 1993. Immune changes during long duration missions. J. Leukocyte Biol. 54: 189-201 18. Sonnenfeld, G., Mandel, A.D., Konstantinova, I.V., Berry, W.D., Taylor, G.R., Lesnyak, A.D., Fuchs, B.B., and Rakhmilevich, A. 1992. Spaceflight alters immune cell function and distribution. J. Appl. Physiol. 73: 191S-195S. 19. Durnova, G.N., Kaplansky, A.S., and Portugalov, V.V. 1977. Effect of 22-day spaceflight on lymphoid organs of rats. Aviat. Space Environ. Med. 47: 588-591. 20. Congdon, C.C., Allebban, Z., Gibson, L.A., Jago, T.L., Strickland, K.M., Johnson, D.L., Lange, R.D., and Ichiki, A.T. 1996. Lymphatic changes in rats flown on Spacelab Life Sciences-2. J. Appl. Physiol. 81: 172-177. 21. Ichiki, A.T., Gibson, L.A., Jago, T.L., Strickland, K.M., Johnson, D.L., Lange, R.D., and Allebban, Z. 1996. Effects of spaceflight on rat peripheral blood leukocytes and bone marrow progenitor cells. J. Leukocyte Biol. 60: 37-43. 22. Mandel, A.D., and Balish, E. 1977. Effect of spaceflight on cell-mediated immunity. Aviat. Space Environ. Med. 48: 1051-1057. 23. Nash, P., Konstantinova, I.V., Fuchs, B., Rakhmilevich, A., Lesynak, A., and Mastro, A.M. 1992. Effect of spaceflight on lymphocyte proliferation and interleukin-2 production. J. Appl. Physiol. 73: 186S-190S. 24. Nash, P., and Mastro, A.M. 1992. Variable lymphocyte responses in rats after spaceflight. Exp. Cell Res. 202: 125-131. 25. Gould, C.L., Lyte, M., Williams, J.A., Mandel, A.D., and Sonnenfeld, G. 1987. Inhibited interferon-gamma but normal interleukin-3 production from rats flown on the Space Shuttle. Aviat. Space Environ. Med. 58:983-986. 26. Miller, E.S., Koebel, D.A., and Sonnenfeld, G. 1995. Influence of spaceflight on the production of interleukin-3 and interleukin-6 by rat spleen and thymus cells. J. Appl. Physiol. 78: 810-813. 27. Sonnenfeld, G. and Miller, E.S. 1993. The role of cytokines in immune changes induced by spaceflight. J. Leukocyte Biol. 54: 253-258. 28. Rykova, M., Sonnenfeld, G., Lesnyak, A.D., Taylor, G.R., Meshkov, D., Mandel, A.D., Medvedev, A., Berry, W.D., Fuchs, B.B., and Konstantinova, I.V. 1992. Effect of spaceflight on natural killer cell activity. J. Appl. Physiol. 73: 196S-200S. 29. Lesnyak, A.D., Sonnenfeld, G., Avery, L., Konstantinova, I.V., Rykova, M., Meshkov, D., and Orlova, T. 1996. Effects of SLS-2 spaceflight on immunologic parameters. J. Appl. Physiol. 81: 178-182. 30. Sonnenfeld, G., Mandel, A.D., Konstantinova, I.V., Taylor, G.R., Berry, W.D., Wellhausen, S.R., Lesnyak, A.T., and Fuchs, B.B. 1990. Effects of spaceflight on levels of activity of immune cells. Aviat. Space Environ. Med. 61: 648-653. 31. Durnova, G.N., Kaplansky, A.S., and Portugalov, V.V. 1997. Effect of 22-day spaceflight on lymphoid organs of rats. Aviat. Space Environ. Med. 47: 588-591.

OCR for page 156
--> 32. Congdon, C.C., Allebban, Z., Gibson, L.A., Kaplansky, A., Strickland, K.M., Jago, T.L., Johnson, D.L., Lange, R.D., and Ichiki, A.T. 1996. Lymphatic changes in rats flown on Spacelab Life Sciences-2. J. Appl. Physiol. 81: 172-177. 33. Ichiki, A.T., Gibson, L.A., Jago, T.L., Strickland, K.M., Johnson, D.L., Lange, R.D., and Allebban, Z. 1996. Effects of spaceflight on rat peripheral blood leukocytes and bone marrow progenitor cells. J. Leukocyte Biol. 60: 37-43. 34. Mandel, A.D., and Balish, E. 1977. Effect of spaceflight on cell-mediated immunity. Aviat. Space Environ. Med. 48: 1051-1057. 35. Nash, P., Konstantinova, I.V., Fuchs, B., Rakhmilevich, A., Lesnyak, A., and Mastro, A.M. 1992. Effect of spaceflight on lymphocyte proliferation and interleukin-2 production. J. Appl. Physiol. 73: 186S-190S. 36. Nash, P., and Mastro, A.M. 1992. Variable lymphocyte responses in rats after spaceflight. Exp. Cell Res. 202: 125-131. 37. Gould, C.L., Lyte, M., Williams, J.A., Mandel, A.D., and Sonnenfeld, G. 1987. Inhibited interferon-gamma but normal interleukin-3 production from rats flown on the Space Shuttle. Aviat. Space Environ. Med. 58: 983-986. 38. Nash, P., Konstantinova, I.V., Fuchs, B., Rakhmilevich, A., Lesnyak, A., and Mastro, A.M. 1992. Effect of spaceflight on lymphocyte proliferation and interleukin-2 production. J. Appl. Physiol. 73: 186S-190S. 39. Nash, P., and Mastro, A.M. 1992. Variable lymphocyte responses in rats after spaceflight. Exp. Cell Res. 202: 125-131. 40. Miller, E.S., Koebel, D.A., and Sonnenfeld, G. 1995. Influence of spaceflight on the production of interleukin-3 and interleukin-6 by rat spleen and thymus cells. J. Appl. Physiol. 78: 810-813. 41. Sonnenfeld, G., and Miller, E.S. 1993. The role of cytokines in immune changes induced by spaceflight. J. Leukocyte Biol. 54: 253-258. 42. Rykova, M., Sonnenfeld, G., Lesnyak, A.D., Taylor, G.R, Meshkov, D., Mandel, A.D., Medvedev, A., Berry, W.D., Fuchs, B.B., and Konstantinova, I.V. 1992. Effect of spaceflight on natural killer cell activity. J. Appl. Physiol. 73: 196S-200S. 43. Lesnyak, A., Sonnenfeld, G., Avery, L., Konstantinova, I., Rykova, M., Meshkov, D., and Orlova, T. 1996. Effect of SLS-2 spaceflight on immunologic parameters. J. Appl. Physiol. 81: 178-182. 44. Lesnyak, A., Sonnenfeld, G., Avery, L., Konstantinova, I., Rykova, M., Meshkov, D., and Orlova, T. 1996. Effect of SLS-2 spaceflighton immunologic parameters . J. Appl. Physiol. 81: 178-182. 45. Sonnenfeld, G., Mandel, A.D., Konstantinova, I.V., Berry, W.D., Taylor, G.R., Lesnyak, A.D., Fuchs, B.B., and Rakhmilevich, A. 1992. Spaceflight alters immune cell function and distribution. J. Appl. Physiol. 73: 191S-195S. 46. Sonnenfeld, G., Mandel, A.D., Konstantinova, I.V., Taylor, G.R., Berry, W.D., Wellhausen, S.R., Lesnyak, A.T., and Fuchs, B.B. 1990. Effects of spaceflight on levels and activity of immune cells. Aviat. Space Environ. Med. 61: 648-653. 47. Sonnenfeld, G., Mandel, A.D., Konstantinova, I.V., Berry, W.D., Taylor, G.R., Lesnyak, A.D., Fuchs, B.B., and Rakhmilevich, A. 1992. Spaceflight alters immune cell function and distribution. J. Appl. Physiol. 73: 191S-195S. 48. Sonnenfeld, G., Mandel, A.D., Konstantinova, I.V., Taylor, G.R., Berry, W.D., Wellhausen, S.R., Lesnyak, A.T., and Fuchs, B.B. 1990. Effects of spaceflight on levels and activity of immune cells. Aviat. Space Environ. Med. 61: 648-653. 49. Sonnenfeld, G., Mandel, A.D., Konstantinova, I.V., Berry, W.D., Taylor, G.R., Lesnyak, A.D., Fuchs, B.B., and Rakhmilevich, A. 1992. Spaceflight alters immune cell function and distribution. J. Appl. Physiol. 73: 191S-195S. 50. Ichiki, A.T., Gibson, L.A., Jago, T.L., Strickland, K.M., Johnson, D.L., Lange, R.D., and Allebban, Z. 1996. Effects of spaceflight on rat peripheral blood leukocytes and bone marrow progenitor cells. J. Leukocyte Biol. 60: 37-43. 51. Sonnenfeld, G., Mandel, A.D., Konstantinova, I.V., Taylor, G.R., Berry, W.D., Wellhausen, S.R., Lesnyak, A.T., and Fuchs, B.B. 1990. Effects of spaceflight on levels and activity of immune cells. Aviat. Space Environ. Med. 61: 648-653. 52. Allebban, Z., Ichiki, A.T., Gibson, L.A., Jones, J.B., Congdon, C.C., and Lange, R.D. 1994. Effects of spaceflight on the number of rat peripheral blood leukocytes and lymphocyte subsets. J. Leukocyte Biol. 55: 209-213. 53. Sonnenfeld, G., Koebel, D.A., and Davis, S. 1995. Effects of hypergravity on immunologic function. Micrograv. Sci. Technol. 7: 323-326. 54. Sonnenfeld, G., Davis, S., Taylor, G.R., Mandel, A.D., Konstantinova, I.V., Lesnyak, A., Fuchs, B.B., Peres, C., Tkackzuk, J., and Schmitt, D.A. 1996. Effect of spaceflight on cytokine production and other immunologic parameters of rhesus monkeys. J. Interferon Cytokine Res. 16: 409-415. 55. Konstantinova, I.V., Rykova, M.P., Lesnyak, A.T., and Antropova,E.A. 1993. Immune changes during long duration missions. J. Leukocyte Biol. 54: 189-201. 56. Taylor, G.R., and Dardano, J.R. 1983. Human cellular responsiveness following spaceflight. Aviat. Space Environ. Med. 54:S55-S59. 57. Taylor, G.R. 1993. Immune changes in short-duration missions. J. Leukocyte Biol. 54: 202-208. 58. Meehan, R.T., Neale, L.S., Kraus, E.T., Stuart, C.A., Smith, M.L., Cintron, N.M., and Sams, C.F. 1992. Alterations in human mononuclear leucocytes following spaceflight. Immunology 76: 491-497.

OCR for page 156
--> 59. Meehan, R.T., Whitson, P., and Sams, C. 1993. The role of psychoneuroendocrine factors on spaceflight-induced immunological alterations. J. Leukocyte Biol. 54: 236-244. 60. Meehan, R.T., Whitson, P., and Sams, C. 1993. The role of psychoneuroendocrine factors on spaceflight-induced immunological alterations. J. Leukocyte Biol. 54: 236-244. 61. Konstantinova, I.V., Rykova, M.P., Lesnyak, A.T., and Antropova, E.A. 1993. Immune changes during long duration missions. J. Leukocyte Biol. 54: 189-201. 62. Konstantinova, I.V., and Fuchs, B.B. 1991. The Immune System in Space and Other Extreme Conditions. Harwood Academic Publishers, Chur, Switzerland. 63. Tálas, M., Bátkai, L. Stöger, I., Nagy, K., Hiros, L., Konstantinova, I., Rykova, M., Mozogovava, J., Gusev, O., and Kozharinov, V. 1984. Results of the space experiment program "Interferon." Acta Astronautica 11: 379-386. 64. Tálas, M., Bátkai, L. Stöger, I., Nagy, K., Hiros, L., Konstantinova, I., Rykova, M., Mozogovava, J., Gusev, O., and Kozharinov, V. 1984. Results of the space experiment program "Interferon." Acta Astronautica 11: 379-386. 65. Konstantinova, I.V., Rykova, M.P., Lesnyak, A.T., and Antropova, E.A. 1993. Immune changes during long duration missions. J. Leukocyte Biol. 54: 189-201. 66. Konstantinova, I.V., and Fuchs, B.B. 1991. The Immune System in Space and Other Extreme Conditions. Harwood Academic Publishers, Chur, Switzerland. 67. Taylor, G.R., and Janney, R.P. 1992. In vivo testing confirms a blunting of the human cell-mediated immune mechanism during spaceflight. J. Leukocyte Biol. 51: 129-132. 68. Gmünder, F.K., Konstantinova, I., Cogoli, A., Lesnyak, A., Bogomolov, W., and Grachov, A.W. 1994. Cellular immunity in cosmonauts during long duration spaceflight on board the orbital MIR station. Aviat. Space Environ. Med. 65: 419-423. 69. Taylor, G.R., and Janney, R.P. 1992. In vivo testing confirms a blunting of the human cell-mediated immune mechanism during spaceflight. J. Leukocyte Biol. 51: 129-132. 70. Gmünder, F.K., Konstantinova, I., Cogoli, A., Lesnyak, A., Bogomolov, W., and Grachov, A.W. 1994. Cellular immunity in cosmonauts during long duration spaceflight on board the orbital MIR station. Aviat. Space Environ. Med. 65: 419-423. 71. Cogoli, A., and Gmünder, F.K. 1991. Gravity effects on single cells: Techniques, findings and theories. Pp. 183-248 in Advances in Space Biology and Medicine, Vol. 1 (S.E. Bonting, ed.). JAI Press, Greenwich, Conn. 72. Cogoli, A., Valuchi-Morf, M., Müller, M., and Breigleb, W. 1980. The effect of hypogravity on human lymphocyte activation. Aviat. Space Environ. Med. 51: 29-34. 73. Cogoli, A., Tschopp, A., and Fuchs-Bislin, P. 1984. Cell sensitivity to gravity. Science 225: 228-230. 74. Cogoli, A. 1993. The effect of hypogravity and hypergravity on cells of the immune system. J. Leukocyte Biol. 54: 259-268. 75. Gmünder, F.K., Kiess, M., Sonnenfeld, G., Lee, J., and Cogoli, A. 1990. A ground-based model to study the effects of weightlessness on lymphocytes. Biol. Cell 70: 33-38. 76. Bechler, H., Cogoli, A., Cogoli-Greuter, M., Müller, O., and Hunzinger, E. 1992. Activation of microcarrier attached lymphocytes in microgravity. Biotechnol. Bioeng. 40: 991-996. 77. Cogoli, A. 1993. The effect of hypogravity and hypergravity on cells of the immune system. J. Leukocyte Biol. 54: 259-268. 78. Chapes, S.K., Morrison, D.R., Guikema, J.A., Lewis, M.L., and Spooner B.S. 1992. Cytokine secretion by immune cells in space. J.Leukocyte Biol. 52: 104-110. 79. Armstrong, J.W., Gerren, R.A., and Chapes S.K. 1995. The effect of space and parabolic flight on macrophage hematopoiesis and function. Exp. Cell Res. 216: 160-168. 80. Limouse, M., Manie, S., Konstantinova, I., Ferrua, B., and Schaffar, L. 1991. Inhibition of phorbol ester-induced activation in microgravity. Exp. Cell Res. 197: 82-86. 81. Schmitt, D.A., Hatton, J.P., Emond, C., Chaput, D., Paris, H., Levade, T., Cazenave, J.P., and Schaffar, L. 1996. The distribution of protein kinase C in human leukocytes is altered in microgravity. FASEB J. 10: 1627-1634. 82. Fleming, S.D., Edelman, L.S., and Chapes, S.K. 1991. Effects of corticosterone and microgravity on inflammatory cell production of superoxide. J. Leukocyte Biol. 50: 69-76. 83. Woods, K.M., and Chapes, S.K. 1994. Abrogation of TNF-mediated cytotoxicity by spaceflight involves protein kinase C. Exp. Cell Res. 211: 171-174. 84. Konstantinova, I.V., Rykova, M.P., Lesnyak, A.T., and Antropova, E.A. 1993. Immune changes during long duration missions. J. Leukocyte Biol. 54: 189-201.

OCR for page 156
--> 85. Konstantinova, I.V., and Fuchs, B.B. 1991. The Immune System in Space and Other Extreme Conditions. Harwood Academic Publishers, Chur, Switzerland. 86. Cogoli, A., and Gmünder, F.K. 1991. Gravity effects on single cells: Techniques, findings and theories. Pp. 183-248 in Advances in Space Biology and Medicine, Vol. 1 (S.E. Bonting, ed.). JAI Press, Greenwich, Conn. 87. Cogoli, A., Valuchi-Morf, M., Müller, M., and Breigleb, W. 1980. The effect of hypogravity on human lymphocyte activation. Aviat. Space Environ. Med. 51: 29-34. 88. Cogoli, A., Tschopp, A., and Fuchs-Bislin, P. 1984. Cell sensitivity to gravity. Science 225: 228-230. 89. Cogoli, A. 1993. The effect of hypogravity and hypergravity on cells of the immune system. J. Leukocyte Biol. 54: 259-268. 90. Bechler, H., Cogoli, A., Cogoli-Greuter, M, Müller, O, and Hunzinger, E. 1992. Activation of microcarrier attached lymphocytes in microgravity. Biotechnol. Bioeng. 40: 991-996. 91. Konstantinova, I.V., and Fuchs, B.B. 1991. The Immune System in Space and Other Extreme Conditions. Harwood Academic Publishers, Chur, Switzerland. 92. LeBlanc, A.D., Schneider, V.S., Evans, H.J., Englebretson, D.A., and Krebs, J.M. 1992. Bone mineral loss and recovery after 17 weeks of bed-rest. J. Bone Miner. Res. 5: 843-850. 93. Cogoli, A., and Gmünder, F.K. 1991. Gravity effects on single cells: Techniques, findings and theories. Pp. 183-248 in Advances in Space Biology and Medicine, Vol. 1 (S.E. Bonting, ed.). JAI Press, Greenwich, Conn. 94. Hargens, A.R., Tipton, C.M., Gollnick, P.D., Mubarak, S.J. Tucker, B.J., and Akeson, W.H. 1983. Fluid shifts and muscle function in humans during acute simulated weightlessness. J. Appl. Physiol. 54: 1003-1009. 95. Konstantinova, I.V., and Fuchs, B.B. 1991. The Immune System in Space and Other Extreme Conditions. Harwood Academic Publishers, Chur, Switzerland. 96. LeBlanc, A.D., Schneider, V.S., Evans, H.J., Englebretson, D.A., and Krebs, J.M. 1992. Bone mineral loss and recovery after 17 weeks of bed-rest. J. Bone Miner. Res. 5: 843-850. 97. Albrecht-Buehler, G. 1992. The simulation of microgravity conditions on the ground. ASGSB Bull. 5: 3-10. 98. Chapes, S.K., Mastro, A.M., Sonnenfeld, G., and Berry, W.D. 1993. Antiorthostatic suspension as a model for the effects of spaceflight on the immune system. J. Leukocyte Biol. 54: 227-235. 99. Musacchia, X.J., Deavers, D., Meininger, G., and Davis, T. 1980. A new model for hypokinesia: Effects on muscle atrophy in the rat. J. Appl. Physiol. 48: 470-476. 100. Chapes, S.K., Mastro, A.M., Sonnenfeld, G., and Berry, W.D. 1993. Antiorthostatic suspension as a model for the effects of spaceflight on the immune system. J. Leukocyte Biol. 54: 227-235. 101. Berry, W.D., Murphy, J., Smith, B., Taylor, G.R., and Sonnenfeld, G. 1991. Effect of microgravity modeling on interferon and interleukin responses in the rat. J. Interferon Res. 11: 243-249. 102. Caren, L., Mandel, A.D., and Nunes, J. 1980. Effect of simulated weightlessness on the immune system in rats. Aviat. Space Environ.Med. 51: 251-255. 103. Rose, A., Steffen, J.M., Musacchia, X.J., Mandel, A.D., and Sonnenfeld, G. 1984. Effect of antiorthostatic suspension on interferon-alpha/beta production by the mouse. Proc. Soc. Exp. Biol. Med. 177: 254-256. 104. Sonnenfeld, G., Mandel, A.D., Konstantinova, I.V., Berry, W.D., Taylor, G.R., Lesnyak, A.D., Fuchs, B.B., and Rakhmilevich, A. 1992. Spaceflight alters immune cell function and distribution. J. Appl. Physiol. 73: 191S-195S. 105. Sonnenfeld, G., Morey, E.R., Williams, J.A., and Mandel, A.D. 1982. Effect of a simulated weightlessness model on the production of rat interferon. J. Interferon Res. 2: 267-270. 106. Chapes, S.K., Mastro, A.M., Sonnenfeld, G., and Berry, W.D. 1993. Antiorthostatic suspension as a model for the effects of spaceflight on the immune system. J. Leukocyte Biol. 54: 227-235. 107. Berry, W.D., Murphy, J., Smith, B., Taylor, G.R., and Sonnenfeld, G. 1991. Effect of microgravity modeling on interferon and interleukin responses in the rat. J. Interferon Res. 11: 243-249. 108. Chapes, S.K., Mastro, A.M., Sonnenfeld, G., and Berry, W.D. 1993. Antiorthostatic suspension as a model for the effects of spaceflight on the immune system. J. Leukocyte Biol. 54: 227-235. 109. Berry, W.D., Murphy, J., Smith, B., Taylor, G.R., and Sonnenfeld, G. 1991. Effect of microgravity modeling on interferon and interleukin responses in the rat. J. Interferon Res. 11: 243-249. 110. Kopydlowski, K.M., McVey, D.S., Woods, K.M., Landolo, J.J., and Chapes, S.K. 1992. Effects of antiorthostatic suspension and corticosterone on macrophage and spleen cell function. J. Leukocyte Biol. 52: 202-208. 111. Nash, P., Bour, B., and Mastro, A. 1991. Effect of hindlimb suspension simulation of microgravity on in vitro immunological responses. Exp. Cell Res. 195: 353-360. 112. Kopydlowski, K.M., McVey, D.S., Woods, K.M., Landolo, J.J., and Chapes, S.K. 1992. Effects of antiorthostatic suspension and corticosterone on macrophage and spleen cell function. J. Leukocyte Biol. 52: 202-208.

OCR for page 156
--> 113. Fleming, S.D., Rosenkrans, C., and Chapes, S.K. 1990. Test of the antiorthostatic suspension model on the inflammatory cell response. Aviat. Space Environ. Med. 61: 327-332. 114. Miller, E.S., Koebel, D.A., Davis, S.A., Klein, J.B., McLeish, K.R., Goldwater D., and Sonnenfeld, G. 1994. Influence of suspension on the oxidative burst by rat neutrophils. J. Appl. Physiol. 76: 387-390. 115. Berry, W.D., Murphy, J., Smith, B., Taylor, G.R., and Sonnenfeld, G. 1991. Effect of microgravity modeling on interferon and interleukin responses in the rat. J. Interferon Res. 11: 243-249. 116. Caren, L., Mandel, A.D., and Nunes, J. 1980. Effect of simulated weightlessness on the immune system in rats. Aviat. Space Environ. Med. 51: 251-255. 117. Nash, P., Bour, B., and Mastro, A. 1991. Effect of hindlimb suspension simulation of microgravity on in vitro immunological responses. Exp. Cell Res. 195: 353-360. 118. Gould, C.L., and Sonnenfeld, G. 1987. Enhancement of viral pathogenesis in mice maintained in an antiorthostatic model: Coordination with effects on interferon production. J. Biol. Regul. Homeost. Agent. 1: 33-36. 119. Gould, C.L., and Sonnenfeld, G. 1987. Enhancement of viral pathogenesis in mice maintained in an antiorthostatic model: Coordination with effects on interferon production. J. Biol. Regul. Homeost. Agent. 1: 33-36. 120. Miller, E.S., and Sonnenfeld, G. 1993. Influence of suspension on the expression of protective immunological memory to murine Listeria monocytogenes infection. J. Leukocyte Biol. 54: 378-383. 121. Miller, E.S., and Sonnenfeld, G. 1994. Influence of antiorthostatic suspension on resistance to murine Listeria monocytogenes infection. J. Leukocyte Biol. 55: 371-378. 122. Gould, C.L., and Sonnenfeld, G. 1987. Enhancement of viral pathogenesis in mice maintained in an antiorthostatic model: Coordination with effects on interferon production. J. Biol. Regul. Homeost. Agent. 1: 33-36. 123. Miller, E.S., and Sonnenfeld, G. 1993. Influence of suspension on the expression of protective immunological memory to murine Listeria monocytogenes infection. J. Leukocyte Biol. 54: 378-383. 124. Miller, E.S., and Sonnenfeld, G. 1994. Influence of antiorthostatic suspension on resistance to murine Listeria monocytogenes infection. J. Leukocyte Biol. 55: 371-378. 125. Konstantinova, I.V., and Fuchs, B.B. 1991. The Immune System in Space and Other Extreme Conditions. Harwood Academic Publishers, Chur, Switzerland. 126. Dick, E.C., Mandel A.D., Warshaver, D.M., Conklin, S.C., and Jerde, R.S. 1977. Respiratory virus transmission at McMurdo Station. Antarctic J. 12: 2-3. 127. Meehan, R.T., Duncan, U., Neale, L., Taylor, G., Muchmore, H., Scott, N., Ramsey, K., Smith, E., Rock, P., Goldblum, R., and Houston, C. 1988. Operation Everest II: Alterations in the immune system at high altitudes. J. Clin. Immunol. 8: 397-403. 128. Schmitt, D.A., and Schaffar, L. 1993. Isolation and confinement as a model for spaceflight immune changes. J. Leukocyte Biol. 54: 209-213. 129. Schmitt, D.A., Peres, C., Sonnenfeld, G., Tkackzuk, J., Arquier, M., Mauco, G., and Ohayon, E. 1995. Immune responses in humans after 60 days of confinement. Brain Behav. Immunol. 9: 70-77. 130. Schmitt, D.A., Schaffar, L., Taylor, G.R., Loftin, K.C., Schneider, V.S., Koebel, A., Abbal, M., Sonnenfeld, G., Lewis, D.E., Reuben, J.R., and Ferebee, R. 1996. Use of bed rest and head-down tilt to simulate spaceflight-induced immune system changes. J. Interferon Cytokine Res. 15: 151-157. 131. Sonnenfeld, G., Measel, J., Loken, M.R., Degioanni, J., Follini, S., Galvagno, A., and Montalbini, M. 1992. Effect of isolation on interferon production and hematological parameters. J. Interferon Res. 12: 75-81. 132. Hargens, A.R., Tipton, C.M., Gollnick, P.D., Mubarak, S.J. Tucker, B.J., and Akeson, W.H. 983. Fluid shifts and muscle function in humans during acute simulated weightlessness. J. Appl. Physiol. 54: 1003-1009. 133. Albrecht-Buehler, G. 1992. The simulation of microgravity conditions on the ground. ASGSB Bull. 5: 3-10. 134. Cogoli, A., and Gmünder, F.K. 1991. Gravity effects on single cells: Techniques, findings and theories. Pp. 183-248 in Advances in Space Biology and Medicine, Vol. 1 (S.E. Bonting, ed.). JAI Press, Greenwich, Conn. 135. Pellis, N.R., Goodwin, T.J., Risin, D., McIntyre, B.W., Pizzini, R.P., Cooper, D., Baker, T.L., and Spaulding, G.F. 1997. Changes in gravity inhibit lymphocyte locomotion through type I collagen. In Vitro Cell Dev. Biol. Anim. 33: 398-405.

OCR for page 156
Part III Additional Space Environment Issues

OCR for page 156
This page in the original is blank.