Download PDF
Int J Sports Med 2000; 21(Supplement 1): 14-19
DOI: 10.1055/s-2000-1454
Georg Thieme Verlag Stuttgart · New York

Exercise and Neuroendocrine Regulation of Antibody Production: Protective Effect of Physical Activity on Stress-InducedSuppression of the Specific Antibody Response

M. Fleshner
  • Department of Kinesiology and Applied Physiology, University of Colorada, Boulder, USA
Further Information

Publication History

Publication Date:
31 December 2000 (online)

Also available at
    Permissions and Reprints

It has been convincingly demonstrated that the in vivo immune response is not fully autonomous. Clearly, functional interactions exist between the neuroendocrine system and the immune system that operate during the generation of normal in vivo immune responses. In addition to playing an important regulatory role in the absence of perturbation, the same neuroendocrine signals that facilitate immune function in a non-stressed organism may suppress immune function in a physiologically or psychologically stressed organism. Given the complexity of these interactions, the current paper will focus on neuroendocrine modulation of one important dimension of acquired immunity, the in vivo antibody response to a benign protein (keyhole limpet hemocyanin, KLH). In addition, only the hypothalamic-pituitary-adrenal (corticosterone) response and the sympathetic nervous system (norepinephrine and epinephrine) response will be discussed. The current paper will 1) examine the cellular steps involved in the antibody response to KLH; 2) describe the specific cellular consequences of acute stressor exposure on this response; 3) describe the evidence for corticosterone and catecholamine modulation of the in vivo antibody response during quiescent and stressed states; and 4) present data that support the hypothesis that regular, moderate, physical activity can prevent the neuroendocrine and detrimental immunological effects of stress.

Key words:

Stress, exercise, antibody response, KLH, neuroendocrine.

References

  • 1 Berlin J A, Colditz G A. A meta-analysis of physical activity in the prevention of coronary heart disease.  Am J Epidemiol. 1990;  132 612-628
    PubMedGoogle Scholar
  • 2 Brown J D, Siegal J M. Exercise as a buffer of life stress: A prospective study of adolescent health.  Health Psych. 1988;  7 341-353
    PubMedGoogle Scholar
  • 3 Chambers C A, Allison J P. Co-stimulation in T cell responses.  Curr Opin Immunol. 1997;  9 396-404
    CrossrefPubMedGoogle Scholar
  • 4 Cross R J, Roszman T L. Central catecholamine depletion impairs in vivo immunity but not in vitro lymphocyte activation.  J Neuroimmunology. 1988;  19 33-45
    PubMedGoogle Scholar
  • 5 Dishman R K, Warren J M, Youngstedt S D, Yoo H, Bunnell B N, Mougey E H, Meyerhoff J L, Joso-Friedmann L, Evans D L. J Appl Physiol 1995 78 (4): 1547-1554
  • 6 Felten D, Felten S, Bellenger D, Carlson S, Ackermann D, Madden K, Olshowka J A, Livnat S. Noradrenergic sympathetic neural interactions with the immune system: Structure and function.  Immunol Rev. 1987;  100 225-260
    PubMedGoogle Scholar
  • 7 Finkelman R E, Holmes J, Katona I M, Urban J F, Beckman M P, Park L S, Schooley K A, Coffman R L, Mosmann T R, Paul W W. Lymphokine control of in vivo immunoglobulin isotype selection.  Ann Rev Immunol. 1990;  8 303-333
    CrossrefPubMedGoogle Scholar
  • 8 Fleshner M, Laudenslager M L, Simons L, Maier S F. Reduced serum antibodies associated with social defeat in rats.  Phys Behav. 1989;  45 1183-1187
    PubMedGoogle Scholar
  • 9 Fleshner M, Watkins L R, Lockwood L L, Bellgrau D, Laudenslager M L, Maier S F. Specific changes in lymphocyte subpopulations: A potential mechanism for stress-induced immunosuppression.  J Neuroimmunol. 1992;  4 131-142
    PubMedGoogle Scholar
  • 10 Fleshner M, Brohm M, Watkins L R, Laudenslager M L, Maier S F. Modulation of the in vivo antibody response by benzodiazepine-inverse agonist (DMCM) given centrally or peripherally.  Phys Behav. 1993;  54 1149-1154
    PubMedGoogle Scholar
  • 11 Fleshner M, Deak T, Spencer R C, Laudenslager M L, Watkins L R, Maier S F. A long-term increase in basal levels of corticosterone and a decrease in corticosteroid binding globulin (CBG) following acute stressor exposure.  Endo. 1995;  136 5336-5342
    PubMedGoogle Scholar
  • 12 Fleshner M, Hermann J, Lockwood L L, Watkins L R, Laudenslager M L, Maier S F. Stressed rats fail to expand the CD45RC+CD4+ (Th1-like) T cell subset in response to KLH: Possible involvementk of IFN-γ.  Brain, Behav Immun. 1995;  9 101-112
    CrossrefPubMedGoogle Scholar
  • 13 Fleshner M, Brennan F X, Watkins L R, Maier S F. RU486 blocks the differentially suppressive effect of stress on the in vivo anti-KLH immunoglobulin response.  Am J Phys. 1996;  271 R1344-R1352
    PubMedGoogle Scholar
  • 14 Fleshner M, Nguyen K T, Deak T, Watkins L R, Maier S F. A normal regulatory role of glucocorticoids in the anti-KLH in vivo antibody response. Psychoneuroimmunology Research Society Abstracts 1997
    Google Scholar
  • 15 Green-Johnson J M, Zalcman S, Vriend C Y, Dolina S, Nance D M, Greenberg A H. Role of norepinephrine in suppressed IgG production in epilepsy-prone mice.  Life Sci. 1996;  59 (14) 1121-1132
    CrossrefPubMedGoogle Scholar
  • 16 Irwin M. Brain corticotropin-releasing hormone and interleukin-1 beta-induced suppression of specific antibody production.  Endo. 1993;  133 (3) 1352-1360
    PubMedGoogle Scholar
  • 17 Laudenslager M L, Fleshner M. Stress and Immunity: Of mice, monkeys, models and mechanics. In: Glaser R, Kiecolt-Glaser J (eds) The Handbook of Human Stress and Immunity. Academic Press 1994: 161-181
    Google Scholar
  • 18 MacNeil B J, Jansen A H, Greenberg A H, Nance D M. Activation and selectivity of splenic sympathetic nerve electrical activity response to bacterial endotoxin.  Am J Phys. 1996;  270 R264-R270
    PubMedGoogle Scholar
  • 19 MacNeil B J, Jansen A H, Janz L J, Greenberg A H, Nance D M. Peripheral endotoxin increases splenic sympathetic nerve activity via central prostaglandin synthesis.  Am J Phys. 1997;  273 R609-R614
    PubMedGoogle Scholar
  • 20 Maier S F, Goehler L E, Fleshner M, Watkins L R. The role of the vagus nerve in cytokine to brain communication.  ANAS. 1998;  840 289-300
    PubMedGoogle Scholar
  • 21 Maier S F, Fleshner M, Watkins L R. Neural, Endocrine and Immune Mechanisms of Stress-Induced Immunomodulation. In: Levy A, Grauer E, Ben-Nathan D, de Kloet ER (eds) New Frontiers in Stress Research: Modulation of Brain Function. Harwood Academic Publishers 1998: 175-185
    Google Scholar
  • 22 Mazzeo R S, Grantham P A. Norepinephrine turnover in various tissues at rest and during exercise: Evidence for a training effect.  Metab. 1989;  38 (4) 479-483
    PubMedGoogle Scholar
  • 23 Miller A H, Spencer R L, Pearce B D, Pisell T L, Tanapat P, Leung J J, Dhabar R S, McEwen B S, Biron C A. Effects of viral infection on corticosterone secretion and glucocorticoid receptor binding in immune tissues.  Psychoneuroendocrinology. 1997;  22 (6) 55-474
    PubMedGoogle Scholar
  • 24 Moraska A, Deak T, Spencer R S, Roth D, Fleshner M. Evidence of chronic stress after forced treadmill but not voluntary freewheel running in rats. Phys Behav 1999 submitted
    Google Scholar
  • 25 Moraska A, Smith T P, Noble E G, Semmler J G, Fleshner M. Physical activity prevents immunological and cellular responses to stress. Soc Neurosci Abstr 1999
    Google Scholar
  • 26 Nieman D C. Risk of upper respiratory tract infection in athletes: An epidemiologic and immunological perspective.  J Athletic Training. 1997;  32 (4) 343-349
    PubMedGoogle Scholar
  • 27 Pedolin D A, Wei Y, Pagliassotti M J. Effects of a high-fat diet and voluntary wheel running on gluconeogenesis and lipolysis in rats.  J Appl Phys. 1999;  86 (4) 1374-1380
    PubMedGoogle Scholar
  • 28 Peters-Futre E M. Vitamin C, neutrophil function, and upper respiratory tract injection risk in distance runners: The missing link.  Exercise Immun Rev. 1997;  3 32-52
    PubMedGoogle Scholar
  • 29 Ramer-Quinn D S, Baker R A, Sanders V M. Activated T helper 1 and T helper 2 cells differentially express the β2-adrenergic receptor: a mechanism for selective modulation of T helper 1 cell cytokine production.  J Immunol. 1997;  159 (10) 4857-4867
    PubMedGoogle Scholar
  • 30 Rogausch H, Del Rey A, Oertel J, Besedovsky H O. Norepinephrine stimulates lymphoid cell mobilization from the perfused rat spleen via β-adrenergic receptors.  Am J Phys. 1999;  276 R724-R730
    PubMedGoogle Scholar
  • 31 Sanders V M, Powell-Oliver F E. β2-Adrenoreceptor stimulation increases the number of antigen-specific precursor B lymphocytes that differentiate into IgM-secreting cells without affecting burst size.  J Immunol. 1992;  148 (6) 1822-1828
    PubMedGoogle Scholar
  • 32 Sanders V M, Baker R A, Ramer-Quinn D S, Kasprowicz D J, Fuchs B A, Street N E. Differential expression of the β2-adrenergic receptor by Th1 and Th2 clones: implications for cytokine production and B cell help.  J Immunol. 1997;  158 (9) 4200-4210
    PubMedGoogle Scholar
  • 33 Smith T A, Moraska A, Higgins K, Mazzeo R S, De Serres S J, Fleshner M. Physical activity prevent tissue catecholamine depletion produced by stress. Society for Neuroscience Abstracts 1999
    Google Scholar
  • 34 Stenzel-Poore M, Vale W W, Rivier C. Relationship between antigen-induced immune stimulation and activation of the hypothalamic-pituitary-adrenal axis in the rat.  Endo. 1993;  132 1313-1318
    PubMedGoogle Scholar
  • 35 Sutton L, Fleshner M, Mazzeo R, Maier S F, Watkins L R. A permissive role of corticosterone in an opioid form of stress-induced analgesia: Blockade of opiate analgesia is not due to stress-induced hormone release.  Brain Res. 1994;  663 19-29
    CrossrefPubMedGoogle Scholar
  • 36 Wan W, Briend 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
  • 37 Wiegers G J, Reul J MHM, Holsboer F, de Kloet E R. Enhancement of rat splenic lymphocyte mitogenesis after short-term pre-exposure to corticosteroids in vitro.  Endo. 1994;  135 (6) 2351-2357
    PubMedGoogle Scholar
  • 38 Zalcman S, Green-Johnson J M, Murray L, Wan W, Nance D M, Greenberg A H. Interleukin-2-induced enhancement of an antigen-specifig IgM plaque-forming cell response is mediated by the symphathetic nervous system.  J Pharm Exp Therap. 1994;  271 977-982
    PubMedGoogle Scholar

Ph. D. Monika Fleshner

Department of Kinesiology and Applied Physiology University of Colorado

Campus Box 354 Boulder, Colorado 80309-0354 USA

Phone: Phone:+ 1 (303) 492-1483

Fax: Fax:+ 1 (303) 492-6778

Email: E-mail:fleshner@spot.colorado.edu

      >