Skip to main navigation menu Skip to main content Skip to site footer

Narrative Review

Vol. 17 No. 1 (2019)

Immune dysfunction in spaceflight and diabetes mellitus – translating space observations to terrestrial disease

December 23, 2018


Introduction: Spaceflight alters normal physiology of cells and tissues seen on Earth. Immune cells and signaling molecules appear to be particularly affected, resulting in changes in leukocyte populations, killing ability and effector function, and signaling molecule response. Akin to spaceflight, diabetes mellitus produces significant immune system dysfunction. Applying observations and interventions from spaceflight to conditions such as diabetes mellitus may help to identify new approaches that combat the high clinical and financial burden of terrestrial disease.
Discussion: A literature review was conducted using PubMed, MEDLINE, and Google Scholar. Papers of immune cells conducted in space and studies on diabetes mellitus-related immune dysfunction were included. Broad themes of immunosuppression were seen in both spaceflight and diabetes mellitus. Effects on lymphocytes, neutrophils, eosinophils, monocytes, fibroblasts, growth factors, and inflammatory factors are presented.
Conclusions: Immune responses to spaceflight and DM are inconsistent. The innate immune system responds similarly to spaceflight and DM. In contrast, the adaptive immune system responds differently to spaceflight than to DM. This difference may be the result of a glucocorticoid dominant response linked to innate suppression and a Th2 lymphocyte shift.
Relevance: Diabetes mellitus causes major morbidity and mortality on Earth. Further research is needed to elucidate mechanisms behind these differences and develop countermeasures for immunosuppression in space with application towards diabetic therapy on earth. Furthermore, commercial spaceflight makes it all the more necessary to elucidate these mechanisms as civilian participants with diabetes mellitus or other immune-altering conditions may be space bound.


  2. Boyle JP, Honeycutt AA, Narayan KMV, Hoerger TJ, Geiss LS, Chen H, et al. Projection of diabetes burden through 2050: Impact of changing demography and disease prevalence in the U.S. Diabetes Care. 2001;24(11):1936–40.
  3. Chawla A, Chawla R, Jaggi S. Microvasular and macrovascular complications in diabetes mellitus: Distinct or continuum? Indian J Endocrinol Metab. 2016;20(4):546.
  4. Ahmed AS, Antonsen EL. Immune and vascular dysfunction in diabetic wound healing. J Wound Care. 2016;25(Sup7):S35–46.
  5. Cogoli A. The effect of space flight on human cellular immunity. Environ Med. 1993;37:107–16.
  6. Crucian B, Babiak-Vazquez A, Johnston S, Pierson DL, Ott CM, Sams C. Incidence of clinical symptoms during long-duration orbital spaceflight. Int J Gen Med. 2016;9:383–91.
  7. Mehta SK, Laudenslager ML, Stowe RP, Crucian BE, Sams CF, Pierson DL. Multiple latent viruses reactivate in astronauts during Space Shuttle missions. Brain Behav Immun. 2014;41(1):210–7.
  8. NASA Marshall Spaceflight Center. Advanced Space Transportation Program: Paving the Highway to Space [Internet]. 2008 [cited 2019 Aug 25]. Available from:
  9. Ploutz-Snyder L. Evaluating countermeasures in spaceflight analogs. J Appl Physiol. 2015 Dec;120(8):915–21.
  10. Alam R, Gorska M. Lymphocytes. J Allergy Clin Immunol. 2003;111(2 Suppl):S476-85.
  11. Battista N, Meloni MA, Bari M, Mastrangelo N, Galleri G, Rapino C, et al. 5-Lipoxygenase-dependent apoptosis of human lymphocytes in the International Space Station: data from the ROALD experiment. FASEB J. 2012;26(5):1791–8.
  12. Maccarrone M, Bari M, Finazzi-Agro A, Meloni MA, Ranalli M, Pippia P, et al. Role of Apoptosis in Lymphocyte Depression (ROALD) - 11.22.16.
  13. Fitzgerald W, Chen S, Walz C, Zimmerberg J, Margolis L, Grivel JC. Immune suppression of human lymphoid tissues and cells in rotating suspension culture and onboard the International Space Station. Vitr Cell Dev Biol Anim. 2009;45(10):622–32.
  14. Starr TK, Jameson SC, Hogquist KA. Positive and negative selection of T cells. Annu Rev Immunol. 2003;21(1):139–76.
  15. Cogoli A. Gravitational physiology of human immune cells: a review of in vivo, ex vivo and in vitro studies. J Gravit Physiol. 1996;3(1):1–9.
  16. Crucian B, Sams C. Immune system dysregulation during spaceflight: clinical risk for exploration-class missions. J Leukoc Biol. 2009;86(5):1017–8.
  17. Crucian BE, Stowe RP, Pierson DL, Sams CF. Immune system dysregulation following short- vs long-duration spaceflight. Aviat Sp Environ Med. 2008;79(9):835–43.
  18. Zhen Y, Sun L, Liu H, Duan K, Zeng C, Zhang L, et al. Alterations of peripheral CD4+CD25+Foxp3+ T regulatory cells in mice with STZ-induced diabetes. Vol. 9, Cellular and Molecular Immunology. 2012. p. 75–85.
  19. Taylor KR, Mills RE, Costanzo AE, Jameson JM. ???? T cells are reduced and rendered unresponsive by hyperglycemia and chronic TNF?? in mouse models of obesity and metabolic disease. PLoS One. 2010;5(7).
  20. Pieper K, Grimbacher B, Eibel H. B-cell biology and development. Vol. 131, Journal of Allergy and Clinical Immunology. 2013. p. 959–71.
  21. Fuchs BB, Medvedev AE. Countermeasures for ameliorating in-flight immune dysfunction. J Leukoc Biol. 1993;54(3):245–52.
  22. Rykova MP. Immune system of Russian cosmonauts after orbital space flights. Hum Physiol. 2013;39(5):557–66.
  23. Boxio R, Dournon C, Frippiat J-P. Effects of a long-term spaceflight on immunoglobulin heavy chains of the urodele amphibian Pleurodeles waltl. J Appl Physiol. 2005;98(3):905–10.
  24. Sakowicz-Burkiewicz M, Kocbuch K, Grden M, Maciejewska I, Szutowicz A, Pawelczyk T. High glucose concentration impairs ATP outflow and immunoglobulin production by human peripheral B lymphocytes: Involvement of P2X7 receptor. Immunobiology. 2013;218(4):591–601.
  25. Herberman RB. Natural killer cells. Annu Rev Med. 1986;37:347–52.
  26. Fuchs BB, Medvedev AE. Countermeasures for ameliorating in-flight immune dysfunction. J Leukoc Biol. 1993;54:245–52.
  27. Irina V, Konstantinova MD. Immune resistance of man in space flights. Acta Astronaut. 1991;23(C):123–7.
  28. Tipton CM, Greenleaf JE, Jackson CG. Neuroendocrine and immune system responses with spaceflights. Med Sci Sports Exerc. 1996;28:988–98.
  29. Mehta SK, Kaur I, Grimm EA, Smid C, Feeback DL, Pierson DL, et al. Decreased non-MHC-restricted (CD56+) killer cell cytotoxicity after spaceflight. J Appl Physiol. 2001;91(4):1814–8.
  30. Berrou J, Fougeray S, Venot M, Chardiny V, Gautier JF, Dulphy N, et al. Natural Killer Cell Function, an Important Target for Infection and Tumor Protection, Is Impaired in Type 2 Diabetes. PLoS One. 2013;8(4).
  31. Rodacki M, Svoren B, Butty V, Besse W, Laffel L, Benoist C, et al. Altered natural killer cells in type 1 diabetic patients. Diabetes. 2007;56(1):177–85.
  32. Lorini R, Moretta A, Valtorta A, d’Annunzio G, Cortona L, Vitali L, Bozzola M SF. Cytotoxic activity in children with insulin-dependent diabetes mellitus. Diabetes Res Clin Pr. 1994;23(1):37–42.
  33. Randolph GJ, Jakubzick C, Qu C. Antigen presentation by monocytes and monocyte-derived cells. Vol. 20, Current Opinion in Immunology. 2008. p. 52–60.
  34. Kaur I, Simons ER, Castro V a., Ott CM, Pierson DL. Changes in monocyte functions of astronauts. Brain Behav Immun. 2005;19:547–54.
  35. Kaur I, Simons ER, Kapadia AS, Ott CM, Pierson DL. Effect of spaceflight on ability of monocytes to respond to endotoxins of gram-negative bacteria. Clin Vaccine Immunol. 2008;15(10):1523–8.
  36. Geerlings SE, Hoepelman AI. Immune dysfunction in patients with diabetes mellitus (DM). FEMS Immunol Med Microbiol. 1999;26:259–65.
  37. Peleg AY, Weerarathna T, McCarthy JS, Davis TME. Common infections in diabetes: Pathogenesis, management and relationship to glycaemic control. Vol. 23, Diabetes/Metabolism Research and Reviews. 2007. p. 3–13.
  38. Wetzler C, Kampfer H, Stallmeyer B, Pfeilschifter J, Frank S. Large and sustained induction of chemokines during impaired wound healing in the genetically diabetic mouse: Prolonged persistence of neutrophils and macrophages during the late phase of repair. J Invest Dermatol. 2000;115:245–53.
  39. Ornitz DM, Itoh N. Fibroblast growth factors. Genome Biol. 2001;2(3):REVIEWS3005.
  40. Elliott RL, Blobe GC. Role of transforming growth factor beta in human cancer. J Clin Oncol. 2005;23(9):2078–93.
  41. Davidson JM, Aquino AM, Woodward SC, Wilfinger WW. Sustained microgravity reduces intrinsic wound healing and growth factor responses in the rat. FASEB J. 1999;13:325–9.
  42. Mirza RE, Fang MM, Ennis WJ, Kohl TJ. Blocking interleukin-1?? induces a healing-associated wound macrophage phenotype and improves healing in type 2 diabetes. Diabetes. 2013;62:2579–87.
  43. Lerman OZ, Galiano RD, Armour M, Levine JP, Gurtner GC. Cellular Dysfunction in the Diabetic Fibroblast: Impairment in Migration, Vascular Endothelial Growth Factor Production, and Response to Hypoxia. Am J Pathol. 2003;162(1):303–12.
  44. Nathan C. Neutrophils and immunity: challenges and opportunities. Nat Rev Immunol. 2006;6(3):173–82.
  45. Michurina T V, Domaratskaya EI, Nikonova TM, Khrushchov NG. Blood and clonogenic hemopoietic cells of newts after the space flight. Adv Space Res. 1996;17:295–8.
  46. Stowe RP, Sams CF, Mehta SK, Kaur I, Jones ML, Feeback DL, et al. Leukocyte subsets and neutrophil function after short-term spaceflight. J Leukoc Biol. 1999;65(February):179–86.
  47. Kaur I, Simons ER, Castro VA, Mark Ott C, Pierson DL. Changes in neutrophil functions in astronauts. Brain Behav Immun. 2004;18:443–50.
  48. Geerlings SE, Hoepelman a I. Immune dysfunction in patients with diabetes mellitus (DM). FEMS Immunol Med Microbiol. 1999;26(3–4):259–65.
  49. Karadayi K, Top C, Gulecek O. The relationship between soluble L-selectin and the development of diabetic retinopathy. Ocul Immunol Inflamm. 2003;11(2):123–9.
  50. Kita H. Eosinophils: Multifaceted biological properties and roles in health and disease. Immunol Rev. 2011;242(1):161–77.
  51. Xu W, Wu HF, Ma SG, Bai F, Hu W, Jin Y, et al. Correlation between peripheral white blood cell counts and hyperglycemic emergencies. Int J Med Sci. 2013;10(6):758–65.
  52. Sorrell JM, Caplan AI. Fibroblast heterogeneity: more than skin deep. J Cell Sci. 2004;117(Pt 5):667–75.
  53. Tairbekov MG, Margolis LB, Baibakov BA, Gabova A V, Dergacheva G V. Growth And Motility Of Cell-Culture In Microgravity Conditions (Experiment Fibroblast). Izv Akad Nauk Seriya Biol. 1994;745–50.
  54. Tairbekov MG. The cell as a gravity-dependent biomechanic system. Aviakosm Ekolog Med. 2000;34:3–17.
  55. Liu Y, Wang E. Transcriptional Analysis of Normal Human Fibroblast Responses to Microgravity Stress. Genomics Proteomics Bioinformatics. 2008;6(1):29–41.
  56. Vacek A, Michurina T V., Serova L V., Rotkovska D, Bartonickova A. Decrease in the number of progenitors of erythrocytes (BFUe, CFUe), granulocytes and macrophages (GM-CFC) in bone marrow of rats after a 14-day flight onboard the Cosmos-2044 biosatellite. Folia Biol (Praha). 1991;37:35–41.
  57. Seitzer U, Bodo M, Müller PK, Açil Y, Bätge B. Microgravity and hypergravity effects on collagen biosynthesis of human dermal fibroblasts. Cell Tissue Res. 1995;282(3):513–7.
  58. Brem H, Tomic-Canic M. Cellular and molecular basis of wound healing in diabetes. J Clin Invest. 2007;117:1219–22.
  59. Loots MAM, Lamme EN, Mekkes JR, Bos JD, Middelkoop E. Cultured fibroblasts from chronic diabetic wounds on the lower extremity (non-insulin-dependent diabetes mellitus) show disturbed proliferation. Arch Dermatol Res. 1999;291:93–9.
  60. Spanheimer RG, Umpierrez GE, Stumpf V. Decreased collagen production in diabetic rats. Diabetes. 1988;37:371–6.
  61. Sims JE, Smith DE. The IL-1 family: regulators of immunity. Nat Rev Immunol. 2010;10(2):89–102.
  62. Akdis M, Burgler S, Crameri R, Eiwegger T, Fujita H, Gomez E, et al. Interleukins, from 1 to 37, and interferon-γ: Receptors, functions, and roles in diseases. Vol. 127, Journal of Allergy and Clinical Immunology. 2011. p. 701–21.
  63. Clark IA. How TNF was recognized as a key mechanism of disease. Cytokine Growth Factor Rev. 2007;18(3–4):335–43.
  64. Liuzzo G, Vallejo AN, Kopecky SL, Frye RL, Holmes DR, Goronzy JJ, et al. Molecular fingerprint of interferon-gamma signaling in unstable angina. Circulation. 2001;103:1509–14.
  65. Semov A, Semova N, Lacelle C, Marcotte R, Petroulakis E, Proestou G, et al. Alterations in TNF- and IL-related gene expression in space-flown WI38 human fibroblasts. FASEB J. 2002;16:899–901.
  66. Nakajima T, Schulte S, Warrington KJ, Kopecky SL, Frye RL, Goronzy JJ, et al. T-cell-mediated lysis of endothelial cells in acute coronary syndromes. Circulation. 2002;105:570–5.
  67. Clark AR. Anti-inflammatory functions of glucocorticoid-induced genes. Mol Cell Endocrinol. 2007;275(1–2):79–97.
  68. Leach CS. Fluid control mechanisms in weightlessness. Aviat Sp Environ Med. 1987;58(9 Pt 2).
  69. Leach CS, Alfrey CP, Suki WN, Leonard JI, Rambaut PC, Inners LD, et al. Regulation of body fluid compartments during short-term spaceflight. J Appl Physiol. 1996;81(1):105–16.
  70. Stowe RP, Pierson DL, Feeback DL, Barrett a D. Stress-induced reactivation of Epstein-Barr virus in astronauts. Neuroimmunomodulation. 2000;8(2):51–8.
  71. NASA. Biomedical Results from SKYLAB. Biomedical. 1977;500.
  72. Gazenko OG, Schulzhenko EB, Grigoriev AI, Atkov OY, Egorov AD. Review of basic medical results of the Salyut-7-Soyuz-T 8-month manned flight. Acta Astronaut. 1988;17(2):155–60.
  73. Grigoriev AI, Bugrov SA, Bogomolov V V., Egorov AD, Polyakov V V., Tarasov IK, et al. Main medical results of extended flights on space station Mir in 1986-1990. Acta Astronaut. 1993;29(8):581–5.
  74. Stein TP, Leskiw MJ, Schluter MD, Donaldson MR, Larina I. Protein kinetics during and after long-duration spaceflight on MIR. Am J Physiol. 1999;276(6 Pt 1):E1014-21.
  75. Elenkov IJ. Glucocorticoids and the Th1/Th2 balance. In: Annals of the New York Academy of Sciences. 2004. p. 138–46.
  76. Spanheimer RG, Umpierrez GE, Stumpf V. Decreased collagen production in diabetic rats. Diabetes. 1988;37(4):371–6.


Download data is not yet available.