Abstract
Exercise at regular intervals is assumed to have a positive effect on immune functions. Conversely, after spaceflight and under simulated weightlessness (e.g., bed rest), immune functions can be suppressed. We aimed to assess the effects of simulated weightlessness (Second Berlin BedRest Study; BBR2-2) on immunological parameters and to investigate the effect of exercise (resistive exercise with and without vibration) on these changes. Twenty-four physically and mentally healthy male volunteers (20–45 years) performed resistive vibration exercise (n=7), resistance exercise without vibration (n=8) or no exercise (n=9) within 60 days of bed rest. Blood samples were taken 2 days before bed rest, on days 19 and 60 of bed rest. Composition of immune cells was analyzed by flow cytometry. Cytokines and neuroendocrine parameters were analyzed by Luminex technology and ELISA/RIA in plasma. General changes over time were identified by paired t-test, and exercise-dependent effects by pairwise repeated measurements (analysis of variance (ANOVA)). With all subjects pooled, the number of granulocytes, natural killer T cells, hematopoietic stem cells and CD45RA and CD25 co-expressing T cells increased and the number of monocytes decreased significantly during the study; the concentration of eotaxin decreased significantly. Different impacts of exercise were seen for lymphocytes, B cells, especially the IgD+ subpopulation of B cells and the concentrations of IP-10, RANTES and DHEA-S. We conclude that prolonged bed rest significantly impacts immune cell populations and cytokine concentrations. Exercise was able to specifically influence different immunological parameters. In summary, our data fit the hypothesis of immunoprotection by exercise and may point toward even superior effects by resistive vibration exercise.
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References
Gleeson M . Immune function in sport and exercise. J Appl Physiol 2007; 103: 693–699.
Kruger K, Mooren FC . Exercise-induced leukocyte apoptosis. Exerc Immunol Rev 2014; 20: 117–134.
Radom-Aizik S, Zaldivar FP Jr, Haddad F, Cooper DM . Impact of brief exercise on circulating monocyte gene and microRNA expression: implications for atherosclerotic vascular disease. Brain Behav Immun 2014; 39: 121–129.
Vitlic A, Lord JM, Phillips AC . Stress, ageing and their influence on functional, cellular and molecular aspects of the immune system. Age (Dordr) 2014; 36: 9631.
Nicogossian AE, Dietlein LF . Microgravity simulation and analogues. In: Nicogossian AE (ed.) Space Physiology and Medicine. Philadelphia, PA: Lea & Febiger, 1982: pp. 240–248.
Belavy DL, Beller G, Armbrecht G, Perschel FH, Fitzner R, Bock O et al. Evidence for an additional effect of whole-body vibration above resistive exercise alone in preventing bone loss during prolonged bed rest. Osteoporos Int 2011; 22: 1581–1591.
Pavy-Le Traon A, Heer M, Narici MV, Rittweger J, Vernikos J . From space to Earth: advances in human physiology from 20 years of bed rest studies (1986–2006). Eur J Appl Physiol 2007; 101: 143–194.
Stein TP, Schluter MD, Moldawer LL . Endocrine relationships during human spaceflight. Am J Physiol 1999; 276: E155–E162.
Shearer WT, Ochs HD, Lee BN, Cohen EN, Reuben JM, Cheng I et al. Immune responses in adult female volunteers during the bed-rest model of spaceflight: antibodies and cytokines. J Allergy Clin Immunol 2009; 123: 900–905.
Schmitt DA, Schaffar L, Taylor GR, Loftin KC, Schneider VS, Koebel A et al. Use of bed rest and head-down tilt to simulate spaceflight-induced immune system changes. J Interferon Cytokine Res 1996; 16: 151–157.
Zwart SR, Crawford GE, Gillman PL, Kala G, Rodgers AS, Rogers A et al. Effects of 21 days of bed rest, with or without artificial gravity, on nutritional status of humans. J Appl Physiol 2009; 107: 54–62.
Uchakin PN, Tobin BW, Morukov BV, Larina IV, Cubbage ML . Type 1 vs. type 2 cytokine secretion in vitro and its regulation by hydrocortisone in humans subjected to 120-day anti-orthostatic bed-rest regime. J Gravit Physiol 2002; 9: 71–82.
Feuerecker M, Feuerecker B, Matzel S, Long M, Strewe C, Kaufmann I et al. Five days of head-down-tilt bed rest induces noninflammatory shedding of L-selectin. J Appl Physiol (1985) 2013; 115: 235–242.
Hamburg NM, McMackin CJ, Huang AL, Shenouda SM, Widlansky ME, Schulz E et al. Physical inactivity rapidly induces insulin resistance and microvascular dysfunction in healthy volunteers. Arterioscler Thromb Vasc Biol 2007; 27: 2650–2656.
Hojbjerre L, Sonne MP, Alibegovic AC, Nielsen NB, Dela F, Vaag A et al. Impact of physical inactivity on adipose tissue low-grade inflammation in first-degree relatives of type 2 diabetic patients. Diabetes Care 2011; 34: 2265–2272.
Schmitt DA, Schwarzenberg M, Tkaczuk J, Hebrard S, Brandenberger G, Mauco G et al. Head-down tilt bed rest and immune responses. Pflugers Arch 2000; 441: R79–R84.
Xu X, Tan C, Li P, Zhang S, Pang X, Liu H et al. Changes of cytokines during a spaceflight analog—a 45-day head-down bed rest. 2013; PLoS One 8: e77401.
Stowe RP, Yetman DL, Storm WF, Sams CF, Pierson DL . Neuroendocrine and immune responses to 16-day bed rest with realistic launch and landing G profiles. Aviat Space Environ Med 2008; 79: 117–122.
Murdaca G, Setti M, Brenci S, Fenoglio D, Lantieri P, Indiveri F et al. Modifications of immunological and neuro-endocrine parameters induced by antiorthostatic bed-rest in human healthy volunteers. Minerva Med 2003; 94: 363–378.
Kanikowska D, Sato M, Iwase S, Shimizu Y, Inukai Y, Nishimura N et al. Immune and neuroendocrine responses to head-down rest and countermeasures. Aviat Space Environ Med 2008; 79: 1091–1095.
Blanc S, Normand S, Pachiaudi C, Duvareille M, Gharib C . Leptin responses to physical inactivity induced by simulated weightlessness. Am J Physiol Regul Integr Comp Physiol 2000; 279: R891–R898.
Ksinantova L, Koska J, Kvetnansky R, Marko M, Hamar D, Vigas M . Effect of simulated microgravity on endocrine response to insulin-induced hypoglycemia in physically fit men. Horm Metab Res 2002; 34: 155–159.
Lovejoy JC, Smith SR, Zachwieja JJ, Bray GA, Windhauser MM, Wickersham PJ et al. Low-dose T3 improves the bed rest model of simulated weightlessness in men and women. Am J Physiol 1999; 277: E370–E379.
Stuart CA, Shangraw RE, Prince MJ, Peters EJ, Wolfe RR . Bed-rest-induced insulin resistance occurs primarily in muscle. Metabolism 1988; 37: 802–806.
Belavý DL, Seibel MJ, Roth HJ, Armbrecht G, Rittweger J, Felsenberg D . The effects of bed-rest and countermeasure exercise on the endocrine system in male adults: evidence for immobilization-induced reduction in sex hormone-binding globulin levels. J Endocrinol Invest 2012; 35: 54–62.
Vernikos J, Dallman MF, Keil LC, O'Hara D, Convertino VA . Gender differences in endocrine responses to posture and 7 days of -6 degrees head-down bed rest. Am J Physiol 1993; 265: E153–E161.
Zorbas YG, Naexu KA, Federenko YF . Blood serum biochemical changes in physically conditioned and unconditioned subjects during bed rest and chronic hyperhydration. Clin Exp Pharmacol Physiol 1992; 19: 137–145.
Ferrando AA, Lane HW, Stuart CA, Davis-Street J, Wolfe RR . Prolonged bed rest decreases skeletal muscle and whole body protein synthesis. Am J Physiol 1996; 270: E627–E233.
Straub RH, Cutolo M, Buttgereit F, Pongratz G . Energy regulation and neuroendocrine—immune control in chronic inflammatory diseases. J Intern Med 2010; 267: 543–560.
Uchakin PN, Stowe RP, Paddon-Jones D, Tobin BW, Ferrando AA, Wolfe RR . Cytokine secretion and latent herpes virus reactivation with 28 days of horizontal hypokinesia. Aviat Space Environ Med 2007; 78: 608–612.
Crucian BE, Stowe RP, Mehta SK, Yetman DL, Leal MJ, Quiriarte HD et al. Immune status, latent viral reactivation, and stress during long-duration head-down bed rest. Aviat Space Environ Med 2009; 80: A37–A44.
Kelsen J, Bartels LE, Dige A, Hvas CL, Frings-Meuthen P, Boehme G et al. 21 Days head-down bed rest induces weakening of cell-mediated immunity—some spaceflight findings confirmed in a ground-based analog. Cytokine 2012; 59: 403–409.
Belavý DL, Bock O, Börst H, Armbrecht G, Gast U, Degner C et al. The 2nd Berlin BedRest Study: protocol and implementation. J Musculoskelet Neuron Interact 2010; 10: 207–219.
Wolfe BL, LeMura LM, Cole PJ . Quantitative analysis of single- vs. multiple-set programs in resistance training. J Strength Condition Res 2004; 18: 35–47.
Belavý DL, Beller G, Armbrecht G, Perschel FH, Fitzner R, Bock O et al. Evidence for an additional effect of whole-body vibration above resistive exercise alone in preventing bone loss during prolonged bed-rest. Osteoporosis Int 2011; 22: 1581–1591.
Harle P, Straub RH, Wiest R, Mayer A, Scholmerich J, Atzeni F et al. Increase of sympathetic outflow measured by neuropeptide Y and decrease of the hypothalamic-pituitary-adrenal axis tone in patients with systemic lupus erythematosus and rheumatoid arthritis: another example of uncoupling of response systems. Ann Rheum Dis 2006; 65: 51–66.
Haider T, Gunga HC, Matteucci-Gothe R, Sottara E, Griesmacher A, Belavy DL et al. Effects of long-term head-down-tilt bed rest and different training regimes on the coagulation system of healthy men. 2013; Physiol Rep 1: e00135.
Norbiato G, Vago T, Battocchio L . Microbial and fungal contamination contributes to physical stress in space flight: studies in the Euromir-95 mission. J Gravit Physiol 1998; 5: P145–P146.
Pierson DL, Stowe RP, Phillips TM, Lugg DJ, Mehta SK . Epstein–Barr virus shedding by astronauts during space flight. Brain Behav Immun 2005; 19: 235–242.
Stowe RP, Peek MK, Cutchin MP, Goodwin JS . Reactivation of herpes simplex virus type 1 is associated with cytomegalovirus and age. J Med Virol 2012; 84: 1797–1802.
Schmitt DA, Schaffar L . Isolation and confinement as a model for spaceflight immune changes. J Leukoc Biol 1993; 54: 209–213.
Mehta SK, Stowe RP, Feiveson AH, Tyring SK, Pierson DL . Reactivation and shedding of cytomegalovirus in astronauts during spaceflight. J Infect Dis 2000; 182: 1761–1764.
Errahali YJ, Thomas LD, Keller TC 3 rd, Lee HJ . Inhibition by new glucocorticoid antedrugs [16alpha, 17alpha-d] isoxazoline and [16alpha, 17alpha-d]-3′-hydroxy-iminoformyl isoxazoline derivatives of chemotaxis and CCL26, CCL11, IL-8, and RANTES secretion. J Interferon Cytokine Res 2013; 33: 493–507.
Lilly CM, Nakamura H, Kesselman H, Nagler-Anderson C, Asano K, Garcia-Zepeda EA et al. Expression of eotaxin by human lung epithelial cells: induction by cytokines and inhibition by glucocorticoids. J Clin Invest 1997; 99: 1767–1773.
Trudel G, Payne M, Madler B, Ramachandran N, Lecompte M, Wade C et al. Bone marrow fat accumulation after 60 days of bed rest persisted 1 year after activities were resumed along with hemopoietic stimulation: the Women International Space Simulation for Exploration study. J Appl Physiol 2009; 107: 540–548.
Dent G, Hadjicharalambous C, Yoshikawa T, Handy RL, Powell J, Anderson IK et al. Contribution of eotaxin-1 to eosinophil chemotactic activity of moderate and severe asthmatic sputum. Am J Respir Crit Care Med 2004; 169: 1110–1117.
Polzer K, Karonitsch T, Neumann T, Eger G, Haberler C, Soleiman A et al. Eotaxin-3 is involved in Churg–Strauss syndrome—a serum marker closely correlating with disease activity. 2008; Rheumatology (Oxford) 47: 804–808.
Marques RE, Guabiraba R, Russo RC, Teixeira MM . Targeting CCL5 in inflammation. Expert Opin Ther Targets 2013; 17: 1439–1460.
Suffee N, Richard B, Hlawaty H, Oudar O, Charnaux N, Sutton A . Angiogenic properties of the chemokine RANTES/CCL5. Biochem Soc Trans 2011; 39: 1649–1653.
Isgro A, Aiuti A, Leti W, Gramiccioni C, Esposito A, Mezzaroma I et al. Immunodysregulation of HIV disease at bone marrow level. Autoimmun Rev 2005; 4: 486–490.
Cocchi F, DeVico AL, Garzino-Demo A, Arya SK, Gallo RC, Lusso P . Identification of RANTES, MIP-1 alpha, and MIP-1 beta as the major HIV-suppressive factors produced by CD8+ T cells. Science 1995; 270: 1811–1815.
Angiolillo AL, Sgadari C, Taub DD, Liao F, Farber JM, Maheshwari S et al. Human interferon-inducible protein 10 is a potent inhibitor of angiogenesis in vivo. J Exp Med 1995; 182: 155–162.
Luster AD, Unkeless JC, Ravetch JV . Gamma-interferon transcriptionally regulates an early-response gene containing homology to platelet proteins. Nature 1985; 315: 672–676.
Booth V, Keizer DW, Kamphuis MB, Clark-Lewis I, Sykes BD . The CXCR3 binding chemokine IP-10/CXCL10: structure and receptor interactions. Biochemistry 2002; 41: 10418–10425.
Dufour JH, Dziejman M, Liu MT, Leung JH, Lane TE, Luster AD . IFN-gamma-inducible protein 10 (IP-10; CXCL10)-deficient mice reveal a role for IP-10 in effector T cell generation and trafficking. J Immunol 2002; 168: 3195–3204.
Buford TW, Willoughby DS . Impact of DHEA(S) and cortisol on immune function in aging: a brief review. Appl Physiol Nutr Metab 2008; 33: 429–433.
Dillon JS . Dehydroepiandrosterone, dehydroepiandrosterone sulfate and related steroids: their role in inflammatory, allergic and immunological disorders. Curr Drug Targets Inflamm Allergy 2005; 4: 377–385.
Ohlsson C, Vandenput L, Tivesten A . DHEA and mortality: What is the nature of the association? J Steroid Biochem Mol Biol 2014; in press.
Pluchino N, Drakopoulos P, Bianchi-Demicheli F, Wenger JM, Petignat P, Genazzani AR . Neurobiology of DHEA and effects on sexuality, mood and cognition. J Steroid Biochem Mol Biol 2014; in press.
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We would like to thank Manuela Jakstadt and Tina Bongrazio for technical assistance.
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Dieter Felsenberg acts as a consultant to the European Space Agency and Novotec Medical for the exploitation of the results of this study. Apart from that, the authors declare no conflict of interest.
The BBR2-2 was supported by grant 14431/02/NL/SH2 from the European Space Agency and grant 50WB0720 from the German Aerospace Center (DLR). The 2nd Berlin Bed rest Study was also sponsored by Novotec Medical, Charité Universitätsmedizin Berlin, Siemens, Osteomedical Group, Wyeth Pharma, Servier Deutschland, P&G, Kubivent, Seca, Astra-Zeneka and General Electric. Daniel L. Belavý was supported by a post-doctoral fellowship from the Alexander von Humboldt Foundation.
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Hoff, P., Belavý, D., Huscher, D. et al. Effects of 60-day bed rest with and without exercise on cellular and humoral immunological parameters. Cell Mol Immunol 12, 483–492 (2015). https://doi.org/10.1038/cmi.2014.106
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DOI: https://doi.org/10.1038/cmi.2014.106
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