Sex differences in stress and immune responses during confinement in Antarctica

C Strewe, D Moser, J-I Buchheim, H-C Gunga, A Stahn, B E Crucian, B Fiedel, H Bauer, P Gössmann-Lang, D Thieme, E Kohlberg, A Choukèr, M Feuerecker, C Strewe, D Moser, J-I Buchheim, H-C Gunga, A Stahn, B E Crucian, B Fiedel, H Bauer, P Gössmann-Lang, D Thieme, E Kohlberg, A Choukèr, M Feuerecker

Abstract

Background: Antarctica challenges human explorers by its extreme environment. The effects of these unique conditions on the human physiology need to be understood to best mitigate health problems in Antarctic expedition crews. Moreover, Antarctica is an adequate Earth-bound analogue for long-term space missions. To date, its effects on human physiology have been studied mainly in male cohorts though more female expeditioners and applicants in astronaut training programs are selected. Therefore, the identification of sex differences in stress and immune reactions are becoming an even more essential aim to provide a more individualized risk management.

Methods: Ten female and 16 male subjects participated in three 1-year expeditions to the German Antarctic Research Station Neumayer III. Blood, saliva, and urine samples were taken 1-2 months prior to departure, subsequently every month during their expedition, and 3-4 months after return from Antarctica. Analyses included cortisol, catecholamine and endocannabinoid measurements; psychological evaluation; differential blood count; and recall antigen- and mitogen-stimulated cytokine profiles.

Results: Cortisol showed significantly higher concentrations in females than males during winter whereas no enhanced psychological stress was detected in both sexes. Catecholamine excretion was higher in males than females but never showed significant increases compared to baseline. Endocannabinoids and N-acylethanolamides increased significantly in both sexes and stayed consistently elevated during the confinement. Cytokine profiles after in vitro stimulation revealed no sex differences but resulted in significant time-dependent changes. Hemoglobin and hematocrit were significantly higher in males than females, and hemoglobin increased significantly in both sexes compared to baseline. Platelet counts were significantly higher in females than males. Leukocytes and granulocyte concentrations increased during confinement with a dip for both sexes in winter whereas lymphocytes were significantly elevated in both sexes during the confinement.

Conclusions: The extreme environment of Antarctica seems to trigger some distinct stress and immune responses but-with the exception of cortisol and blood cell counts-without any major relevant sex-specific differences. Stated sex differences were shown to be independent of enhanced psychological stress and seem to be related to the environmental conditions. However, sources and consequences of these sex differences have to be further elucidated.

Keywords: Antarctica; Confinement; Extreme environment; Immunity; Neuroendocrine response; Sex differences.

Conflict of interest statement

Ethics approval and consent to participate

The participation in the study was voluntary and every subject gave its written informed consent which was approved by the Ethical Board of the University of Munich, Germany (Reference Nr.: 332-08, 524-15). During the whole season, they retained the right to end their participation without any explanation. Applied procedures and techniques were performed in accordance to the Declaration of Helsinki and met the criteria of standard laboratory guidelines and regulations.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Cortisol in saliva in the morning (a) and evening (b) and its ratio between morning and evening samples (c); data are means ± SEM; units are μg/dl; female n = 8–10; male n = 13–16. BDC, baseline data collection; PDC, post data collection; #, significant difference between male and female; +, significant difference to BDC in males
Fig. 2
Fig. 2
Norepinephrine (a, b) and epinephrine (c, d) in urine during the day and night (collection time 12 h); data are means ± SEM; units are μg; female n = 6–10; male n = 11–16. BDC, baseline data collection; PDC, post data collection; #, significant difference between males and females
Fig. 3
Fig. 3
Endocannabinoid and N-acylethanolamide concentrations in lithium-heparinized blood. a, b ECs. c–e NAEs. Data are means ± SEM; units are ng/ml; female n = 9–10; male n = 15–16. BDC, baseline data collection; PDC, post data collection; AEA, anandamide; 2-AG, 2-arachidonoylglycerol; OEA, oleoylethanolamide; PEA, palmitoylethanolamide; SEA, stearoylethanolamide; #, significant difference between male and female; +, significant difference to BDC in males; *, significant difference to BDC in females
Fig. 4
Fig. 4
Blood cell count from EDTA anti-coagulated blood. a Hemoglobin [units are g/dl]. b Hematocrit [units are %]. c Thrombocytes [units are G/l]. d Leukocytes [units are G/l]. e Percentage of granulocytes [units are %]. f Percentage of lymphocytes [units are %]; data are means ± SEM; female n = 6–10; male n = 11–16. BDC, baseline data collection; PDC, post data collection; #, significant difference between male and female; +, significant difference to BDC in males; *, significant difference to BDC in females
Fig. 5
Fig. 5
Cytokine release after stimulation with fungal antigens from lithium-heparinized blood. a Interferon γ (IFN-γ); female n = 9–10; male n = 16. b Interleukin 10 (IL-10); female n = 5–6; male n = 11. c Interleukin 2 (IL-2); female n = 9–10; male n = 16. d TNF (tumor necrosis factor); female n = 9–10; male n = 16; data are means ± SEM; units are pg/ml. BDC baseline data collection; PDC, post data collection; #, significant difference between male and female; +, significant difference to BDC in males; *, significant difference to BDC in females
Fig. 6
Fig. 6
Cytokine release after stimulation with pokeweed mitogen (PWM) from lithium-heparinized blood. a Interferon γ (IFN-γ); female n = 9–10; male n = 16. b Interleukin 10 (IL-10); female n = 5–6; male n = 11. c Interleukin 2 (IL-2); female n = 9–10; male n = 16. d TNF (tumor necrosis factor); female n = 9–10; male n = 16; data are means ± SEM; units are pg/ml. BDC, baseline data collection; PDC post data collection; *, significant difference to BDC in females

References

    1. Suedfeld P, Weiss K. Antarctica natural laboratory and space analogue for psychological research. Environ Behav. 2000;32(1):7–17.
    1. Tanaka M, Watanabe S. Overwintering in the Antarctica as an analog for long term manned spaceflight. Adv Space Res. 1994;14(8):423–430.
    1. Pagel JI, Chouker A. Effects of isolation and confinement on humans-implications for manned space explorations. J Appl Physiol (1985) 2016;120(12):1449–1457.
    1. Arendt J, Middleton B. Human seasonal and circadian studies in Antarctica (Halley, 75 degrees S) Gen Comp Endocrinol. 2018;258:250–258.
    1. Steinach M, et al. Changes of 25-OH-vitamin D during overwintering at the German Antarctic Stations Neumayer II and III. PLoS One. 2015;10(12):e0144130.
    1. Arendt J. Biological rhythms during residence in polar regions. Chronobiol Int. 2012;29(4):379–394.
    1. Mairesse O, MacDonald-Nethercott E, Neu D, Tellez HF, Dessy E, Neyt X, Meeusen R, Pattyn N. Preparing for Mars: human sleep and performance during a 13 month stay in Antarctica. Sleep. 2019;42(1):1–12. 10.1093/sleep/zsy206.
    1. Palinkas LA, et al. Incidence of psychiatric disorders after extended residence in Antarctica. Int J Circumpolar Health. 2004;63(2):157–168.
    1. Chen N, et al. Different adaptations of Chinese winter-over expeditioners during prolonged Antarctic and sub-Antarctic residence. Int J Biometeorol. 2016;60(5):737–747.
    1. Palinkas LA, et al. A randomized placebo-controlled clinical trial of the effectiveness of thyroxine and triiodothyronine and short-term exposure to bright light in prevention of decrements in cognitive performance and mood during prolonged Antarctic residence. Clin Endocrinol. 2010;72(4):543–550.
    1. Yadav AP, et al. Wintering in Antarctica: impact on immune response of Indian expeditioners. Neuroimmunomodulation. 2012;19(6):327–333.
    1. Feuerecker M, Crucian BE, Quintens R, Buchheim JI, Salam AP, Rybka A, Moreels M, Strewe C, Stowe R, Mehta S, Schelling G, Thiel M, Baatout S, Sams C, Choukèr A. Immune sensitization during one year in the Antarctic high altitude Concordia Environment. Allergy. 2019;74(1):64–77. 10.1111/all.13545. Epub 2018 Nov 20.
    1. Feuerecker M, et al. Early adaption to the antarctic environment at dome C: consequences on stress-sensitive innate immune functions. High Alt Med Biol. 2014;15(3):341–348.
    1. Crucian BE, et al. Immune system dysregulation during spaceflight: potential countermeasures for deep space exploration missions. Front Immunol. 2018;9:1437.
    1. Bigley AB, Agha NH, Baker FL, Spielmann G, Kunz HE, Mylabathula PL, Rooney B, Laughlin MS, Pierson DL, Mehta SK, Crucian BE, Simpson RJ. NK-cell function is impaired during long-duration spaceflight. J Appl Physiol (1985). 2018. 10.1152/japplphysiol.00761.2018. [Epub ahead of print].
    1. Mehta SK, et al. Latent virus reactivation in astronauts on the international space station. NPJ Microgravity. 2017;3:11.
    1. Abdullah M, et al. Gender effect on in vitro lymphocyte subset levels of healthy individuals. Cell Immunol. 2012;272(2):214–219.
    1. Uppal SS, Verma S, Dhot PS. Normal values of CD4 and CD8 lymphocyte subsets in healthy Indian adults and the effects of sex, age, ethnicity, and smoking. Cytometry B Clin Cytom. 2003;52(1):32–36.
    1. Teixeira D, et al. Evaluation of lymphocyte levels in a random sample of 218 elderly individuals from Sao Paulo city. Rev Bras Hematol Hemoter. 2011;33(5):367–371.
    1. Klein SL, Flanagan KL. Sex differences in immune responses. Nat Rev Immunol. 2016;16(10):626–638.
    1. Mark S, et al. The impact of sex and gender on adaptation to space: executive summary. J Women's Health (Larchmt) 2014;23(11):941–947.
    1. Strewe C, et al. Modulations of neuroendocrine stress responses during confinement in Antarctica and the role of hypobaric hypoxia. Front Physiol. 2018;9:1647.
    1. Müller B, Basler HD. Kurzfragebogen zur aktuellen Beanspruchung. Gottingen: Beltz Test Gesellschaft; 1993.
    1. Spielberger CD, et al. Manual for the state-trait anxiety inventory. Palo Alto: Consulting Psychologists Press, Inc.; 1970.
    1. Vogeser M, et al. Release of anandamide from blood cells. Clin Chem Lab Med. 2006;44(4):488–491.
    1. Di Marzo V, et al. Role of insulin as a negative regulator of plasma endocannabinoid levels in obese and nonobese subjects. Eur J Endocrinol. 2009;161(5):715–722.
    1. Laux L., G.P., Schaffner P., Spielberger C., Das State-Trait-Angst-Inventar, STAI. 1981. 1. Aufl. Beltz, Weinheim.
    1. Caparros-Gonzalez RA, et al. Hair cortisol levels, psychological stress and psychopathological symptoms as predictors of postpartum depression. PLoS One. 2017;12(8):e0182817.
    1. Eisenberger NI, et al. Neural pathways link social support to attenuated neuroendocrine stress responses. Neuroimage. 2007;35(4):1601–1612.
    1. Hill EE, et al. Exercise and circulating cortisol levels: the intensity threshold effect. J Endocrinol Investig. 2008;31(7):587–591.
    1. Uhart M, et al. Gender differences in hypothalamic-pituitary-adrenal (HPA) axis reactivity. Psychoneuroendocrinology. 2006;31(5):642–652.
    1. Dockray S, Steptoe A. Chronotype and diurnal cortisol profile in working women: differences between work and leisure days. Psychoneuroendocrinology. 2011;36(5):649–655.
    1. Kudielka BM, Bellingrath S, Hellhammer DH. Further support for higher salivary cortisol levels in “morning” compared to “evening” persons. J Psychosom Res. 2007;62(5):595–596.
    1. Randler C, Schaal S. Morningness-eveningness, habitual sleep-wake variables and cortisol level. Biol Psychol. 2010;85(1):14–18.
    1. Yamanaka Y, Motoshima H, Uchida K. Hypothalamic-pituitary-adrenal axis differentially responses to morning and evening psychological stress in healthy subjects. Neuropsychopharmacol Rep. 2019;39(1):41–7. 10.1002/npr2.12042. Epub 2018 Nov 27.
    1. Bonato M, et al. Salivary cortisol concentration after high-intensity interval exercise: time of day and chronotype effect. Chronobiol Int. 2017;34(6):698–707.
    1. Raikkonen K, et al. Poor sleep and altered hypothalamic-pituitary-adrenocortical and sympatho-adrenal-medullary system activity in children. J Clin Endocrinol Metab. 2010;95(5):2254–2261.
    1. Leproult R, et al. Sleep loss results in an elevation of cortisol levels the next evening. Sleep. 1997;20(10):865–870.
    1. Hirotsu C, Tufik S, Andersen ML. Interactions between sleep, stress, and metabolism: from physiological to pathological conditions. Sleep Sci. 2015;8(3):143–152.
    1. Wright KP, Jr, et al. Influence of sleep deprivation and circadian misalignment on cortisol, inflammatory markers, and cytokine balance. Brain Behav Immun. 2015;47:24–34.
    1. Spiegel K, Leproult R, Van Cauter E. Impact of sleep debt on metabolic and endocrine function. Lancet. 1999;354(9188):1435–1439.
    1. Rodenbeck A, Hajak G. Neuroendocrine dysregulation in primary insomnia. Rev Neurol (Paris) 2001;157(11 Pt 2):S57–S61.
    1. Steinach M, et al. Sleep quality changes during overwintering at the German Antarctic Stations Neumayer II and III: the gender factor. PLoS One. 2016;11(2):e0150099.
    1. Dlugos A, et al. Acute stress increases circulating anandamide and other N-acylethanolamines in healthy humans. Neuropsychopharmacology. 2012;37(11):2416–2427.
    1. Hanlon EC, et al. Sleep restriction enhances the daily rhythm of circulating levels of endocannabinoid 2-arachidonoylglycerol. Sleep. 2016;39(3):653–664.
    1. Hauer D, et al. The role of glucocorticoids, catecholamines and endocannabinoids in the development of traumatic memories and posttraumatic stress symptoms in survivors of critical illness. Neurobiol Learn Mem. 2014;112:68–74.
    1. Surkin PN, et al. Pharmacological augmentation of endocannabinoid signaling reduces the neuroendocrine response to stress. Psychoneuroendocrinology. 2018;87:131–140.
    1. Evanson NK, et al. Fast feedback inhibition of the HPA axis by glucocorticoids is mediated by endocannabinoid signaling. Endocrinol. 2010;151(10):4811–4819.
    1. Handa RJ, Weiser MJ. Gonadal steroid hormones and the hypothalamo-pituitary-adrenal axis. Front Neuroendocrinol. 2014;35(2):197–220.
    1. Seale JV, et al. Organizational role for testosterone and estrogen on adult hypothalamic-pituitary-adrenal axis activity in the male rat. Endocrinology. 2005;146(4):1973–1982.
    1. Handa RJ, et al. Gonadal steroid hormone receptors and sex differences in the hypothalamo-pituitary-adrenal axis. Horm Behav. 1994;28(4):464–476.
    1. Babb JA, et al. Sex differences in activated corticotropin-releasing factor neurons within stress-related neurocircuitry and hypothalamic-pituitary-adrenocortical axis hormones following restraint in rats. Neuroscience. 2013;234:40–52.
    1. Figueiredo HF, et al. Estrogen potentiates adrenocortical responses to stress in female rats. Am J Physiol Endocrinol Metab. 2007;292(4):E1173–E1182.
    1. Viau V, Meaney MJ. Variations in the hypothalamic-pituitary-adrenal response to stress during the estrous cycle in the rat. Endocrinology. 1991;129(5):2503–2511.
    1. Heck AL, Handa RJ. Sex differences in the hypothalamic–pituitary–adrenal axis’ response to stress: an important role for gonadal hormones. Neuropsychopharmacology. 2019;44(1):45–58.
    1. Oyola MG, Handa RJ. Hypothalamic-pituitary-adrenal and hypothalamic-pituitary-gonadal axes: sex differences in regulation of stress responsivity. Stress. 2017;20(5):476–494.
    1. Bangasser DA, Valentino RJ. Sex differences in stress-related psychiatric disorders: neurobiological perspectives. Front Neuroendocrinol. 2014;35(3):303–319.
    1. Kudielka BM, Kirschbaum C. Sex differences in HPA axis responses to stress: a review. Biol Psychol. 2005;69(1):113–132.
    1. Kirschbaum C, et al. Impact of gender, menstrual cycle phase, and oral contraceptives on the activity of the hypothalamus-pituitary-adrenal axis. Psychosom Med. 1999;61(2):154–162.
    1. Seeman TE, et al. Gender differences in age-related changes in HPA axis reactivity. Psychoneuroendocrinology. 2001;26(3):225–240.
    1. Ricart A, et al. Sex-linked differences in pulse oxymetry. Br J Sports Med. 2008;42(7):620–621.
    1. Levental S, et al. Sex-linked difference in blood oxygen saturation. Clin Respir J. 2018;12(5):1900–1904.
    1. Feuerecker M, et al. A corticoid-sensitive cytokine release assay for monitoring stress-mediated immune modulation. Clin Exp Immunol. 2013;172(2):290–299.
    1. Shearer WT, et al. Suppression of human anti-inflammatory plasma cytokines IL-10 and IL-1RA with elevation of proinflammatory cytokine IFN-gamma during the isolation of the Antarctic winter. J Allergy Clin Immunol. 2002;109(5):854–857.
    1. Dimitrov S, et al. Differential TNF production by monocyte subsets under physical stress: blunted mobilization of proinflammatory monocytes in prehypertensive individuals. Brain Behav Immun. 2013;27(1):101–108.
    1. Gane JM, Stockley RA, Sapey E. TNF-alpha autocrine feedback loops in human monocytes: the pro- and anti-inflammatory roles of the TNF-alpha receptors support the concept of selective TNFR1 blockade in vivo. J Immunol Res. 2016;2016:1079851.
    1. Yi B, et al. 520-d isolation and confinement simulating a flight to Mars reveals heightened immune responses and alterations of leukocyte phenotype. Brain Behav Immun. 2014;40:203–210.
    1. Bowers SL, et al. Stressor-specific alterations in corticosterone and immune responses in mice. Brain Behav Immun. 2008;22(1):105–113.
    1. Solianik R, et al. Similar cold stress induces sex-specific neuroendocrine and working memory responses. Cryo Letters. 2015;36(2):120–127.
    1. Solianik R, et al. Gender-specific cold responses induce a similar body-cooling rate but different neuroendocrine and immune responses. Cryobiology. 2014;69(1):26–33.
    1. LaVoy EC, McFarlin BK, Simpson RJ. Immune responses to exercising in a cold environment. Wilderness Environ Med. 2011;22(4):343–351.
    1. Pongor V, et al. Systemic and immunomodulatory effects of whole body therapeutic hypothermia. Orv Hetil. 2011;152(15):575–580.
    1. Walsh NP, Whitham M. Exercising in environmental extremes : a greater threat to immune function? Sports Med. 2006;36(11):941–976.
    1. Kimberly WT, et al. Sex differences and hemoglobin levels in relation to stroke outcomes. Neurology. 2013;80(8):719–724.
    1. Murphy WG. The sex difference in haemoglobin levels in adults - mechanisms, causes, and consequences. Blood Rev. 2014;28(2):41–47.
    1. Jaremo P, Milovanivic M, Richter A. Gender and stable angina pectoris: women have greater thrombin-evoked platelet activity but similar adenosine diphosphate-induced platelet responses. Thromb Haemost. 2005;94(1):227–228.
    1. Jaremo P, Eriksson-Franzen M, Milovanovic M. Platelets, gender and acute cerebral infarction. J Transl Med. 2015;13:267.
    1. Johnson M, Ramey E, Ramwell PW. Sex and age differences in human platelet aggregation. Nature. 1975;253(5490):355–357.
    1. Stuijver DJ, et al. Incidence of venous thromboembolism in patients with Cushing’s syndrome: a multicenter cohort study. J Clin Endocrinol Metab. 2011;96(11):3525–3532.
    1. Van Zaane B, et al. Hypercoagulable state in Cushing's syndrome: a systematic review. J Clin Endocrinol Metab. 2009;94(8):2743–2750.

Source: PubMed

Sponzoři a spolupracovníci

Zdravotní podmínky

Drogové intervence

3
Předplatit