Download PDF
Int J Sports Med 2000; 21(Supplement 1): 20-23
DOI: 10.1055/s-2000-1447
Georg Thieme Verlag Stuttgart · New York

Exercise Immunology: Neuroendocrine Regulation of NK-Cells

I. H. Jonsdottir
  • Institute of Physiology and Pharmacology, Department of Physiology, Göteborg University, Sweden
Further Information

Publication History

Publication Date:
31 December 2000 (online)

Also available at
    Permissions and Reprints

Natural immunity, including that of the natural killer (NK) cells, is strongly influenced by physical exercise, but the physiological significance of the reported changes in NK cells after exercise training is as yet unclear. The exercise effect is likely mediated by interactions between the central nervous and endocrine systems. Chronic activation of endogenous opioid systems augments natural cytotoxicity. We have investigated the possible involvement of opioids in the exercise-induced enhancement of NK cell function. The pathways by which the central nervous system may communicate with the periphery include neuroendocrine outflow via the hypothalamic-pituitary-adrenal axis and the autonomic nervous system (ANS) through direct nerve fiber connections with cells or the organs of the immune system. This review will discuss the role of various neuroendocrine factors such as growth hormone, catecholamines and glucocorticoids and the role of the ANS, in particular the sympathetic division, in modulating NK cell function in response to exercise.

Key words:

Catecholamines, endogenous opioids, exercise, HPA-axis, NK cells.

References

  • 1 Baslund B, Lyngberg K, Andersen V, Halkjaer-Kristensen J, Hansen M, Klokker M, Pedersen B K. Effect of 8 wk of bicycle training on the immune system of patients with rheumatoid arthritis.  J Appl Physiol. 1993;  75 (4) 1691-1695
    PubMedGoogle Scholar
  • 2 Bellinger D L, Felten S Y, Lorton D, Felten D L. Origin of noradrenergic innervation of the spleen in rats.  Brain, Behavior and Immunity. 1989;  3 291-311
    CrossrefPubMedGoogle Scholar
  • 3 Benschop R J, Oostveen F G, Heijnen C J, Ballieux R E. β2-Adrenergic stimulation causes detachment of natural killer cells from cultured endothelium.  Eur J Immunol. 1993;  23 3242-3247
    PubMedGoogle Scholar
  • 4 Besedovsky H O, Del Ray A, Sorkin E, Da Prada M, Keller H H. Immunoregulation mediated by the sympathetic nervous system.  Cell Immunol. 1979;  48 346-355
    CrossrefPubMedGoogle Scholar
  • 5 Blake M J, Stein E A, Vomachka A J. Effects of exercise training on brain opioid peptides and serum LH in female rats.  Peptides. 1984;  5 953-958
    CrossrefPubMedGoogle Scholar
  • 6 Blalock J E, Bost K L, Smith E M. Neuroendocrine peptide hormones and their receptors in the immune system.  J Neuroimmunol. 1985;  10 31-40
    CrossrefPubMedGoogle Scholar
  • 7 Carr D JJ. The role of endogenous opioids and their receptors in the immune system.  Proc Soc Experm Biolog Med. 1991;  198 710-720
    PubMedGoogle Scholar
  • 8 Christ D M, Mackinnon L T, Thompson R F, Atterbom H A, Egan P A. Physical exercise increases natural cellular-mediated tumor cytotoxicity in elderly women.  Gerontology. 1989;  35 66-71
    PubMedGoogle Scholar
  • 9 Croiset G, Heijnen C J, van der Wal W E, de Boer S F, de Wied D. A role for the autonomic nervous system in modulating the immune response during mild emotional stimuli.  Life Sci. 1990;  46 419-425
    CrossrefPubMedGoogle Scholar
  • 10 de Meirleir K, Naaktgeboren N, Van Steirteghem A, Gorus F, Olbrecht J, Block P. β-Endorphin and ACTH levels in peripheral blood during and after aerobic and anaerobic exercise.  Eur J Appl Physiol. 1986;  55 5-8
    PubMedGoogle Scholar
  • 11 Farrell P A, Kjaer M, Bach F W, Galbo H. β-Endorphin and adrenocorticotropin response to supramaximal treadmill exercise in trained and untrained males.  Acta Physiol Scand. 1987;  130 619-625
    PubMedGoogle Scholar
  • 12 Felten D L, Felten S Y, Bellinger D L, Carlson S L, Ackerman K D, Madden K S, Olschowki J A, Livnat S. Noradrenergic sympathetic neural interactions with the immune system: structure and function.  Immunological Reviews. 1987;  100 225-260
    PubMedGoogle Scholar
  • 13 Galant S P, Underwood S, Duriseti L, Insel P A. Characterization and high affinity of β2-adrenergic receptor binding by (-)-[3H]-dihydroprenolol binding to human polymorphonuclear particulates.  J Lab Clin Med. 1978;  92 613-618
    PubMedGoogle Scholar
  • 14 Gannon G A, Shek P N, Shephard R J. Natural killer cells: Modulation by intensity and duration of exercise.  Exerc Immunol Rev. 1995;  1 26-48
    PubMedGoogle Scholar
  • 15 Gatti G, Masera R G, Pallavicini L, Sartori M L, Staurenghi A, Orlandi F, Angeli A. Interplay in vitro between ACTH, β-endorphin, and glucocorticoids in the modulation of spontaneous and lymphokine-inducible human natural killer (NK) cell activity.  Brain Behav Immun. 1993;  7 16-28
    CrossrefPubMedGoogle Scholar
  • 16 Heijnen C J, Kavelaars A, Ballieux R E. β-Endorphin: cytokine and neuropeptide.  Immunol Rev. 1991;  119 42-63
    PubMedGoogle Scholar
  • 17 Herberman R B, Reynolds C W, Ortaldo J R. Mechanism of cytotoxictiy by natural killer (NK) cells.  Ann Rev Immunol. 1986;  4 651-680
    CrossrefPubMedGoogle Scholar
  • 18 Hoffmann P, Terenius L, Thorén P. Cerebrospinal fluid immunoreactive β-endorphin concentration is increased by voluntary exercise in spontaneously hypertensive rat.  Regulatory Peptides. 1990;  28 233-239
    CrossrefPubMedGoogle Scholar
  • 19 Jankovic B D, Radulovic J. Enkephalins, brain and immunity: Modulation of immune responses by methionine-enkephalin injected into the cerebral cavity.  Intern J Neuroscience. 1992;  67 241-270
    PubMedGoogle Scholar
  • 20 Jonsdottir I H, Asea A, Hoffmann P, Hellstrand K, Thorén P. Voluntary chronic exercise augments in vivo cytotoxicity in rats.  J Appl Physiol. 1996;  80 1799-1803
    PubMedGoogle Scholar
  • 21 Jonsdottir I H, Johansson C, Asea A, Johansson P, Hellstrand K, Thorén P, Hoffmann P. Duration and mechanism of the increased natural cytotoxicity seen after chronic voluntary exercise in rats.  Acta Physiol Scand. 1997;  160 333-339
    CrossrefPubMedGoogle Scholar
  • 22 Kay N, Allen J, Morley J E. Endorphins stimulate normal human peripheral blood lymphocyte natural killer activity.  Life Sciences. 1984;  35 53-59
    CrossrefPubMedGoogle Scholar
  • 23 Lewis C E, McGee J O. Natural killer cells in tumour biology. In: Lewis CE, McGee JO (eds) The Natural Killer Cell. Oxford; IRL press at Oxford university press 1992: 175-203
    Google Scholar
  • 24 MacNeil B, Hoffman-Goetz L. Chronic exercise enhances in vivo and in vitro cytotoxic mechanisms of natural immunity in mice.  J Appl Physiol. 1993;  74 388-395
    PubMedGoogle Scholar
  • 25 Madden K S, Felten D L. Experimental basis for neural-immune interactions.  Physiological Reviews. 1995;  75 77-106
    PubMedGoogle Scholar
  • 26 Mandler R N, Biddison W E, Mandler R, Serrate S A. β-Endorphin augments the cytolytic activity and interferon production of natural killer cells.  J Immunol. 1986;  136 (3) 934-939
    PubMedGoogle Scholar
  • 27 Mathews P M, Froelich C J, Sibbitt W L, Bankhurst A D. Enhancement of natural cytotoxicity by β-endorphin.  J Immunol. 1983;  130 1658-1662
    PubMedGoogle Scholar
  • 28 Metzger J M, Stein E A. β-Endorphin and sprint training.  Life Sci. 1984;  34 1541-1547
    CrossrefPubMedGoogle Scholar
  • 29 Mitchell J H. Neural control of the circulation during exercise.  Med Sci Sports Exerc. 1990;  22 141-154
    PubMedGoogle Scholar
  • 30 Morley J E, Kay N E, Solomon G F, Plotnikoff N P. Neuropeptides: Conductors of the immune orchestra.  Life Sciences. 1987;  41 527-544
    CrossrefPubMedGoogle Scholar
  • 31 Mörch H, Pedersen B K. β-Endorphin and the immune system - possible role in autoimmune diseases.  Autoimmunity. 1995;  21 161-171
    PubMedGoogle Scholar
  • 32 Nieman D C, Henson D A, Gusewitch G, Warren B J, Dotson R C, Butterworth D E, Nehlsen-Cannarella S L. Physical activity and immune function in elderly women.  Med Sci Sports Exerc. 1993;  25 823-831
    PubMedGoogle Scholar
  • 33 Nieman D C, Miller A R, Henson D A, Warren B J, Gusewitch G, Johnson R L, Nehlsen-Cannarella S L. Effects of high- vs. moderate-intensity exercise on natural killer cell activity.  Med Sci Sports Exerc. 1993;  25 (10) 1126-1134
    PubMedGoogle Scholar
  • 34 Nieman D C, Nehlsen-Cannarella S L, Markoff P A, Balk-Lamberton A J, Yang H, Chritton D BW, Lee J W, Arabatzis K. The effects of moderate exercise training on natural killer cells and acute upper respiratory tract infections.  Int J Sports Med. 1990;  11 467-473
    PubMedGoogle Scholar
  • 35 O'Shea J, Ortaldo J R. The biology of natural killer cells: insights into the molecular basis of function. In: Lewis CE, McGee JO (eds) The Natural Killer Cell. Oxford; Oxford University Press 1992 1: 2-40
    Google Scholar
  • 36 Pedersen B K, Nielsen H B. Acute exercise and the immune system. In: Pedersen BK (ed) Exercise Immunology. Heidelberg, Germany; Springer 1997 2: 5-38
    Google Scholar
  • 37 Przewlocki R. Opioid systems and stress. In: Herz A (ed) Opioids II. Berlin, Heidelberg; Springer-Verlag 1993 42: 293-324
    Google Scholar
  • 38 Rouveix B. Opiates and immune function.  Therapie. 1992;  47 503-512
    PubMedGoogle Scholar
  • 39 Trinchieri G. Biology of natural killer cells.  Adv Immunol. 1989;  47 187-376
    PubMedGoogle Scholar
  • 40 Tvede N, Kappel M, Halkjaer-Kristensen J, Galbo H, Pedersen B K. The effect of light, moderate and severe bicycle exercise on lymphocyte subsets, natural and lymphokine activated killer cells, lymphocyte proliferative response and interleukin-2 production.  Int J Sports Med. 1993;  14 (5) 275-282
    Article in Thieme ConnectPubMedGoogle Scholar
  • 41 Ullum H, Palmö J, Halkjaer-Kristensen J, Diamant M, Klokker M, Kruuse A, LaPerriere A, Klarlund Pedersen B. The effect of acute exercise on lymphocyte subsets, natural killer cells, proliferative responses, and cytokines in HIV-seropositive persons.  J Acquir Immune Defic Syndr. 1994;  7 1122-1133
    PubMedGoogle Scholar
  • 42 Wan W, Vriend C Y, Wetmore L, Gartner J G, Greenberg A H, Nance D M. The effects of stress on splenic immune function are mediated by the splenic nerve.  Brain Res Bull. 1993;  30 101-105
    CrossrefPubMedGoogle Scholar
  • 43 Weber R J, Pert A. The periaqueductal gray matter mediates opiate-induced immunosuppression.  Science. 1989;  245 188-190
    PubMedGoogle Scholar
  • 44 Weigent D A, Blalock J E. Interactions between the neuroendocrine and immune systems: Common hormones and receptors.  Immunological Reviews. 1987;  100 79-108
    PubMedGoogle Scholar
  • 45 Weigent D A, Blalock J E. Associations between the neuroendocrine and immune systems.  J Leukocyte Biol. 1995;  57 137-150
    PubMedGoogle Scholar
  • 46 Welsh R M, Vargas-Cortes M. Natural killer cells in viral infections. In: Lewis CE, McGee JO (eds) The natural killer cell. Oxford; Oxford University Press 1992 4: 107-150
    Google Scholar
  • 47 Wilmore J H, Costill D L. Physiology of sport and exercise. Champaign, USA; Human Kinetics 1994
    Google Scholar

I . H. Jonsdottir

Institute of Physiology and Pharmacology Department of Physiology

Box 432 40530 Göteborg Sweden

Phone: Phone:+ 46 (31) 7733527

Fax: Fax.+ 46 (31) 7733512

Email: E-mail:inga.jons@fysiologi.gu.se

      >