Biology Bulletin Reviews

, Volume 8, Issue 6, pp 482–488 | Cite as

Immunomodulating Effects of Cold Stress

  • S. V. GeinEmail author
  • I. L. Sharav’eva


Cold stress is an indispensable environmental factor that exerts effects on various functions of organisms, including immune regulation. The paper provides integral data on the effects of cold stress on indices of innate and adaptive immunity.


cold stress innate immunity lymphocytes macrophages cytokines 



  1. 1.
    Avakyan, A.R., Lazarev, A.I., Prokopenko, L.G., and Uteshev, B.S., Immunomodulatory effect of activators of carbohydrate and lipid metabolism in acute cold stress, Eksp. Klin. Farmakol., 2002, vol. 65, no. 3, pp. 50–53.Google Scholar
  2. 2.
    Aviles, H., Johnson, M.T., and Monroy, F.P., Effects of cold stress on spleen cell proliferation and cytokine production during chronic Toxoplasma gondii infection, Neuroimmunomodulation, 2004, vol. 11, pp. 93–102.CrossRefGoogle Scholar
  3. 3.
    Baccan, G.C., Oliveira, R.D., and Mantovani, B., Stress and immunological phagocytosis: possible nongenomic action of corticosterone, Life Sci., 2004, vol. 75, no. 11, pp. 1357–1368.CrossRefGoogle Scholar
  4. 4.
    Baccan, G.C., Sesti-Costa, R., Chedraoui-Silva, S., and Mantovani, B., Effects of cold stress, corticosterone and catecholamines on phagocytosis in mice: differences between resting and activated macrophages, Neuroimmunomodulation, 2010, vol. 17, no. 6, pp. 379–385.CrossRefGoogle Scholar
  5. 5.
    Beilin, B., Shavit, Y., Razumovsky, J., et al., Effects of mild perioperative hypothermia on cellular immune responses, Anesthesiology, 1998, vol. 89, pp. 1133–1140.CrossRefGoogle Scholar
  6. 6.
    Belay, T. and Woart, A., Cold-induced stress increases the intensity of Chlamydia genital infection in mice, J. Microbiol. Immunol. Infect., 2013, vol. 46, no. 5, pp. 330–337.CrossRefGoogle Scholar
  7. 7.
    Beukel van den, J.C., Grefhorst, A., Quarta, C., et al., Direct activating effects of adrenocorticotropic hormone (ACTH) on brown adipose tissue are attenuated by corticosterone, FASEB J., 2014, vol. 28, no. 11, pp. 4857–4867.Google Scholar
  8. 8.
    Bowers, S.L., Bilbo, S.D., Dhabhar, F.S., and Nelson, R.J., Stressor-specific alterations in corticosterone and immune responses in mice, Brain, Behav., Immun., 2008, vol. 22, pp. 105–113.CrossRefGoogle Scholar
  9. 9.
    Brenner, I.K., Castellani, J.W., Gabaree, C., et al., Immune changes in humans during cold exposure: effects of prior heating and exercise, J. Appl. Physiol., 1999, vol. 87, no. 2, pp. 699–710.CrossRefGoogle Scholar
  10. 10.
    Cadet, P., Zhu, W., Mantione, K.J., et al., Cold stress alters Mytilus edulis pedal ganglia expression of mu opiate receptor transcripts determined by real-time RT-PCR and morphine levels, Brain Res.: Mol. Brain Res., 2002, vol. 99, no. 1, pp. 26–33.Google Scholar
  11. 11.
    Cao, L., Filipov, N.M., and Lawrence, D.A., Sympathetic nervous system plays a major role in acute cold/restraint stress inhibition of host resistance to Listeria monocytogenes, J. Neuroimmunol., 2002, vol. 125, nos. 1–2, pp. 94–102.Google Scholar
  12. 12.
    Chebaani, N., Guardiola, F.A., Sihem, M., et al., Innate humoral immune parameters in Tilapia zillii under acute stress by low temperature and crowding, Fish Physiol. Biochem., 2014, vol. 40, no. 3, pp. 797–804.CrossRefGoogle Scholar
  13. 13.
    Cheng, G.J., Morrow-Tesch, J.L., Beller, D.I., et al., Immunosuppression in mice induced by cold water stress, Brain, Behav., Immun., 1990, vol. 4, pp. 278–291.CrossRefGoogle Scholar
  14. 14.
    Dai, M.X., Zheng, X.H., Yu, J., et al., The impact of intermittent and repetitive cold stress exposure on endoplasmic reticulum stress and instability of atherosclerotic plaques, Cell Physiol. Biochem., 2014, vol. 34, no. 2, pp. 393–404.CrossRefGoogle Scholar
  15. 15.
    Dugué, B. and Leppänen, E., Adaptation related to cytokines in man: effects of regular swimming in ice-cold water, Clin. Physiol., 2000, vol. 20, no. 2, pp. 114–121.Google Scholar
  16. 16.
    Elenkov, I.J., Wilder, R.L., Chrousos, G.P., and Vizi, E.S., The sympathetic nerve—an integrative interface between two supersystems: the brain and the immune system, Pharmacol. Rev., 2000, vol. 52, no. 4, pp. 595–638.Google Scholar
  17. 17.
    Eliseeva, L.S., Khramova, G.M., Gonsales, E.V., and Kozyreva, T.V., α1- and β-adrenoblockers effects on immunogenesis in rats under thermoneutral conditions and after cooling of various extent, Bull. Exp. Biol. Med., 2009, vol. 147, no. 2, pp. 208–212.CrossRefGoogle Scholar
  18. 18.
    Gein, S.V. and Sharav’eva, I.L., Effect of blockade of opioid receptors on antigenigenesis and proliferative response of splenocytes in stress, Eksp. Klin. Farmakol., 2013, vol. 76, no. 1, pp. 30–34.Google Scholar
  19. 19.
    Gein, S.V. and Sharavieva, I.L., Effect of rotation and immobilization stress on IL-1β, IL-2, IL-4, and IFN-γ production by splenocytes under opiate receptor blockade in vivo, Dokl. Biol. Sci., 2014, vol. 454, no. 1, pp. 69–71.CrossRefGoogle Scholar
  20. 20.
    Gein, S.V. and Sharav’eva, I.L., Effects of cold stress on the functional activity of mouse peritoneal macrophages in conditions of opiate receptor blockade, Neurosci. Behav. Physiol., 2017a, vol. 47, no. 5, pp. 524–527.CrossRefGoogle Scholar
  21. 21.
    Gein, S.V. and Sharav’eva, I.L., Chronic cold stress modulates the function of peritoneal macrophages in vivo, Dokl. Biol. Sci., 2017b, vol. 474, no. 1, pp. 129–131.CrossRefGoogle Scholar
  22. 22.
    Giagnoni, G., Santagostino, A., Senini, R., et al., Cold stress in the rat induces parallel changes in plasma and pituitary levels of endorphin and ACTH, Pharmacol. Res. Commun., 1983, vol. 15, no. 1, pp. 15–21.CrossRefGoogle Scholar
  23. 23.
    Girotti, M., Donegan, J.J., and Morilak, D.A., Chronic intermittent cold stress sensitizes neuroimmune reactivity in the rat brain, Psychoneuroendocrinology, 2011, vol. 36, no. 8, pp. 1164–1174.CrossRefGoogle Scholar
  24. 24.
    Hangalapura, B.N., Nieuwland, M.G., de Vries, R.G., et al., Effects of cold stress on immune responses and body weight of chicken lines divergently selected for antibody responses to sheep red blood cells, Poult. Sci., 2003, vol. 82, no. 11, pp. 1692–1700.CrossRefGoogle Scholar
  25. 25.
    Hangalapura, B.N., Kaiser, M.G., Poel, J.J., et al., Cold stress equally enhances in vivo pro-inflammatory cytokine gene expression in chicken lines divergently selected for antibody responses, Dev. Comp. Immunol., 2006, vol. 30, pp. 503–511.CrossRefGoogle Scholar
  26. 26.
    Jain, S., Bruot, B.C., and Stevenson, J.R., Cold swim stress leads to enhanced splenocyte responsiveness to concanavalin A, decreased serum testosterone, and increased serum corticosterone, glucose, and protein, Life Sci., 1996, vol. 59, no. 3, pp. 209–218.CrossRefGoogle Scholar
  27. 27.
    Jansky, L., Pospisilova, D., Honzova, S., et al., Immune system of cold-exposed and cold-adapted humans, Eur. J. Appl. Physiol. Occup. Physiol., 1996, vol. 72, nos. 5–6, pp. 445–450.Google Scholar
  28. 28.
    Jurankova, E., Jezova, D., and Vigas, M., Central stimulation of hormone release and the proliferative response of lymphocytes in humans, Mol. Chem. Neuropathol., 1995, vol. 25, pp. 213–223.CrossRefGoogle Scholar
  29. 29.
    Kim, H.G., Lee, J.S., Han, J.M., et al., Myelophil attenuates brain oxidative damage by modulating the hypothalamus-pituitary-adrenal (HPA) axis in a chronic cold-stress mouse model, J. Ethnopharmacol., 2013, vol. 148, no. 2, pp. 505–514.CrossRefGoogle Scholar
  30. 30.
    Kizaki, T., Yamashita, H., Oh-Ishi, S., et al., Immunomodulation by cells of mononuclear phagocyte lineage in acute cold-stressed or cold-acclimatized mice, Immunology, 1995, vol. 86, no. 3, pp. 456–462.Google Scholar
  31. 31.
    Kizaki, T., Oh-Ishi, S., and Ohno, H., Acute cold stress induces suppressor macrophages in mice, J. Appl. Physiol., 1996, vol. 81, no. 1, pp. 393–399.CrossRefGoogle Scholar
  32. 32.
    Kizaki, T., Suzuki, K., Hitomi, Y., et al., Activation and apoptosis of murine peritoneal macrophages by acute cold stress, Biochem. Biophys. Res. Commun., 2001, vol. 283, pp. 700–706.CrossRefGoogle Scholar
  33. 33.
    Korneva, E.A. and Shkhinek, E.K., Gormony i immunnaya sistema (Hormones and Immune Systems), Leningrad: Nauka, 1988.Google Scholar
  34. 34.
    Korneva, E.A., Novikova, N.S., and Rybakina, E.G., Stress-related immunodeficiencies and their correction, VICh-Infekts. Immunosupressii, 2010, vol. 2, no. 3, pp. 23–36.Google Scholar
  35. 35.
    Lackovic, V., Borecký, L., Vigas, M., and Rovenský, J., Activation of NK cells in subjects exposed to mild hyper- or hypothermic load, J. Interferon Res., 1988, vol. 8, pp. 393–402.CrossRefGoogle Scholar
  36. 36.
    Lishmanov, Yu.B., Maslov, L.N., Naryzhnaya, N.V., et al., Endogenous opioid system as a link of urgent and long-term adaptation of the organism to extreme conditions: prospective clinical use of opioid peptides, Vestn. Ross. Akad. Med. Nauk, 2012, no. 6, pp. 73–82.Google Scholar
  37. 37.
    Makarova, O.V., Trunova, G.V., Diatroptov, M.E., et al., Comparative characterization of cytokine production by concanavalin A-activated splenocytes from BALB/c and C57Bl/6 mice after cold exposure, Bull. Exp. Biol. Med., 2005, vol. 139, no. 2, pp. 220–222.Google Scholar
  38. 38.
    McEwen, B.S., Biron, C.A., Brunson, K.W., et al., The role of adrenocorticoids as modulators of immune function in health and disease: neural, endocrine and immune interactions, Brain Res.: Brain Res. Rev., 1997, vol. 23, nos. 1–2, pp. 79–133.Google Scholar
  39. 39.
    Obut, T.A., Saryg, S.K., Grigor’eva, T.A., and Dement’eva, T.Yu., Effect of dehydroepiandrosterone sulfate on aldosterone level during stress exposures: role of μ-opioid receptors, Bull. Exp. Biol. Med., 2012a, vol. 152, no. 6, pp. 696–698.CrossRefGoogle Scholar
  40. 40.
    Obut, T.A., Saryg, S.K., Ovsukova, M.V., et al., Effect of dehydroepiandrosterone sulfate on aldosterone level during stress exposures: role of μ-opioid receptors, Bull. Exp. Biol. Med., 2012b, vol. 152, no. 6, pp. 696–698.CrossRefGoogle Scholar
  41. 41.
    Retana-Márquez, S., Vigueras-Villaseñor, R.M., Juárez-Rojas, L., et al., Sexual behavior attenuates the effects of chronic stress in body weight, testes, sexual accessory glands, and plasma testosterone in male rats, Horm. Behav., 2014, vol. 66, no. 5, pp. 766–778.Google Scholar
  42. 42.
    Rybakina, E.G., Shanin, S.N., Kozinets, I.A., et al., Cellular mechanisms of cold stress-related immunosuppression and the action of interleukin, Int. J. Tissue React., 1997, vol. 19, nos. 3–4, pp. 135–140.Google Scholar
  43. 43.
    Rybakina, E.G., Shanin, S.N., Fomicheva, E.E., et al., The activity of protective functions of the organism under stress and their correction with the drug derinat, Med. Immunol., 2008, vol. 10, pp. 431–438.CrossRefGoogle Scholar
  44. 44.
    Salman, H., Bergman, M., Bessler, H., et al., Hypothermia affects the phagocytic activity of rat peritoneal macrophages, Acta Physiol. Scand., 2000, vol. 68, no. 3, pp. 431–436.CrossRefGoogle Scholar
  45. 45.
    Salmi, P., Kela, J., Arvidsson, U., and Wahlestedt, C., Functional interactions between δ- and μ-opioid receptors in rat thermoregulation, Eur. J. Pharmacol., 2003, vol. 458, nos. 1–2, pp. 101–106.Google Scholar
  46. 46.
    Sandhu, M.A., Zaib, A., Anjum, M.S., and Qayyum, M., Empirical evidence of cold stress induced cell mediated and humoral immune response in common myna (Sturnus tristis), Int. J. Biometeorol., 2015, vol. 59, no. 11, pp. 1607–1613.CrossRefGoogle Scholar
  47. 47.
    Selye, H., Syndrome produced by diverse nocuous agents, Nature, 1936, vol. 138, no. 3479, p. 32.CrossRefGoogle Scholar
  48. 48.
    Sesti-Costa, R., Baccan, G.C., Chedraoui-Silva, S., and Mantovani, B., Effects of acute cold stress on phagocytosis of apoptotic cells: the role of corticosterone, Neuroimmunomodulation, 2010, vol. 17, pp. 79–87.CrossRefGoogle Scholar
  49. 49.
    Sesti-Costa, R., Ignacchiti, M.D., Chedraoui-Silva, S., et al., Chronic cold stress in mice induces a regulatory phenotype in macrophages: correlation with increased 11β-hydroxysteroid dehydrogenase expression, Brain, Behav., Immun., 2012, vol. 26, no. 1, pp. 50–60.Google Scholar
  50. 50.
    Shevchuk, N.A. and Radoja, S., Possible stimulation of anti-tumor immunity using repeated cold stress: a hypothesis, Infect. Agent Cancer , 2007, vol. 13, pp. 2–20.Google Scholar
  51. 51.
    Shu, J., Stevenson, J.R., and Zhou, X., Modulation of cellular immune responses by cold water swim stress in the rat, Dev. Comp. Immunol., 1993, vol. 17, pp. 357–371.CrossRefGoogle Scholar
  52. 52.
    Smith, E.M., Neuropeptides as signal molecules in common with leukocytes and the hypothalamic-pituitary-adrenal axis, Brain, Behav., Immun., 2008, vol. 22, pp. 3–14.CrossRefGoogle Scholar
  53. 53.
    Solianik, R., Skurvydas, A., Vitkauskien\({{\dot {e}}}\), A., and Brazaitis, M., Gender-specific cold responses induce a similar body-cooling rate but different neuroendocrine and immune responses, Cryobiology, 2014, vol. 69, no. 1, pp. 26–33.CrossRefGoogle Scholar
  54. 54.
    Suckow, M.A., Terril, L.A., Grigdesby, C.F., and March, P.A., Evaluation of hypothermia-induced analgesia and influence of opioid antagonists in leopard frogs (Rana pipiens), Pharmacol. Biochem. Behav., 1999, vol. 63, no. 1, pp. 39–43.CrossRefGoogle Scholar
  55. 55.
    Sugama, S., Takenouchi, T., Fujita, M., et al., Cold stress induced morphological microglial activation and increased IL-1β expression in astroglial cells in rat brain, J. Neuroimmunol., 2011, vol. 233, pp. 29–36.CrossRefGoogle Scholar
  56. 56.
    Tringali, G., Farrace, S., Ragazzoni, E., et al., Circulating interleukin-1-beta levels after acute and prolonged exposure to low temperatures: human and rat studies, Neuroimmunomodulation, 2000, vol. 7, pp. 177–181.CrossRefGoogle Scholar
  57. 57.
    Vaswani, K.K., Richard, C.W., and Tejwani, G.A., Cold swim stress-induced changes in the levels of opioid peptides in the rat CNS and peripheral tissues, Pharmacol. Biochem. Behav., 1988, vol. 29, no. 1, pp. 163–168.CrossRefGoogle Scholar
  58. 58.
    Willemsen, G., Carroll, D., Ring, C., and Drayson, M., Cellular and mucosal immune reactions to mental and cold stress: associations with gender and cardiovascular reactivity, Psychophysiology, 2002, vol. 39, no. 2, pp. 222–228.CrossRefGoogle Scholar
  59. 59.
    Zhang, Z., Chen, B., Yuan, L., and Niu, C., Acute cold stress improved the transcription of pro-inflammatory cytokines of Chinese soft-shelled turtle against Aeromonas hydrophila, Dev. Comp. Immunol., 2015, vol. 49, no. 1, pp. 127–137.CrossRefGoogle Scholar
  60. 60.
    Zhao, F.Q., Zhang, Z.W., Yao, H.D., et al., Effects of cold stress on mRNA expression of immunoglobulin and cytokine in the small intestine of broilers, Res. Vet. Sci., 2013, vol. 95, pp. 146–155.CrossRefGoogle Scholar
  61. 61.
    Zhao, F.Q., Zhang, Z.W., Qu, J.P., et al., Cold stress induces antioxidants and Hsps in chicken immune organs, Cell Stress Chaperones, 2014, vol. 19, pp. 635–648.CrossRefGoogle Scholar

Copyright information

© Pleiades Publishing, Ltd. 2018

Authors and Affiliations

  1. 1.Institute of Ecology and Genetics of Microorganisms, Ural Branch of the Russian Academy of SciencesPermRussia
  2. 2.Perm State UniversityPermRussia

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