Int J Sports Med 2000; 21(Supplement 1): 24-30
DOI: 10.1055/s-2000-1448
Georg Thieme Verlag Stuttgart · New York

Exercise and Neuroendocrine Modulation of Macrophage Function

J. A. Woods
  • Department of Kinesiology, University of Illinois, Urbana, Champaign, USA
Further Information

Publication History

Publication Date:
31 December 2000 (online)

Like all immune cells, Mφ's cannot simply be viewed as individual cells, but as part of a complex network of cells and tissues that communicate in many different ways in an attempt to elicit an appropriate host response to immune and other challenges. Mφ's are important initial effector cells and are highly regulated by other cells (including T and B lymphocytes) and hormones produced by the sympathetic nervous system (SNS) and hypothalamic-pituitary-adrenal (HPA) axis. Indeed, it may well be that stressors, including exercise, exert their regulatory influence over these cells by activating the SNS, HPA axis, or by influencing other tissues or cells. With this in mind, the overall objective of this review is to introduce and provide current information regarding the role of neuroendocrine factors in mediating exercise-induced changes in macrophage (Mφ) function. Under this broad objective this review will: 1) briefly discuss the cell biology of the Mφ and its role in host defense, 2) explore the potential regulatory influence of selected neuroendocrine hormones (glucocorticoids, catecholamines, growth hormone, prolactin, and β-endorphin) that may potentially mediate exercise-induced changes in Mφ function, and 3) describe the effects of exercise on the functions of the Mφ.

References

  • 1 Adams D O, Hamilton T A. The cell biology of macrophage activation.  Annu Rev Immunol. 1984;  2 283-318
  • 2 Ahlborg A, Ahlborg G. Exercise leukocytosis with and without β-adrenergic blockade.  Acta Med Scand. 1970;  187 241-246
  • 3 Benedetto N, Folgore A, Galdiero M, Meli R, DiCarlo R. Effect of prolactin, rIFN-γ or rTNF-α in murine toxoplasmosis.  Pathologie Biologie. 1995;  43 395-400
  • 4 Bernton E W, Meltzer M S, Holaday J W. Suppression of macrophage activation and T-lymphocyte function in hypoprolactinemic mice.  Science. 1988;  239 401-404
  • 5 Bernton E W, Bryant H U, Holaday J W. Prolactin and immune function. In: Ader R, Felten D, Cohen N (eds) Psychoneuroimmunology (2nd Ed). New York; Academic Press 1991: 403-428
  • 6 Beutler B N, Krochin N, Milsark I W, Luedke C, Cerami A. Control of cachectin (tumor necrosis factor) synthesis: mechanisms of endotoxin resistance.  Science. 1984;  232 997-1000
  • 7 Boehm U, Klamp T, Groot M, Howard J C. Cellular responses to interferon-γ.  Annu Rev Immunol. 1997;  15 749-795
  • 8 Bosenberg A T, Brock-Utne J G, Gaffin S L, Wells M TB, Blake G TW. Strenuous exercise causes systemic endotoxemia.  J Appl Physiol. 1988;  65 106-108
  • 9 Brenner I KM, Shek P N, Shephard R J. Heat exposure and immune function: Potential contribution to the exercise response.  Exerc Immunol Rev. 1995;  1 49-80
  • 10 Brown S L, van Epps D E. Opioid peptides modulate production of interferon-γ by human mononuclear cells.  Cellular Immunol. 1986;  103 19-26
  • 11 Cannon J G, Kluger M J. Exercise enhances survival rate in mice infected with Salmonella typhimurium.  Proc Soc Exp Biol Med. 1984;  175 518-521
  • 12 Casellas A M, Guardiola H, Renaud F L. Inhibition of opioids of phagocytosis in peritoneal macrophages.  Neuropeptides. 1991;  18 35-40
  • 13 Ceddia M A, Woods J A. Exercise suppresses macrophage antigen presentation.  J Appl Physiol. 1999;  87 (6) 2253-2258
  • 14 Chen Y, Bradley S N. Aging and eliciting agents: effect on murine peritoneal macrophage monokine bioactivity.  Expt Gerontol. 1993;  28 145-159
  • 15 Chen Y, Johnson A G. In vivo activation of macrophages by prolactin from young and aging mice.  Int J Immunopharmacol. 1993;  15 39-45
  • 16 Dardenne M, Carmo Leite de Moraes M, Kelly P A, Gagnerault M. Prolactin receptor expression in human hematopoetic tissues analyzed by flow cytofluorometry.  Endocrinology. 1994;  134 2108-2114
  • 17 Davies J M, Kohut M L, Jackson D A, Hertler-Colbert L M, Mayer E P, Ghaffar A. Execise effects on lung tumor metastases and in vitro alveolar macrophage anti-tumor cytotoxicity.  Am J Physiol. 1998;  274 R1454-R1459
  • 18 De La Fuente M, Martin M I, Ortega E. Changes in the phagocytic function of peritoneal macrophages from old mice after strenuous physical exercise.  Comp Immun Microbiol Infect Dis. 1990;  13 189-198
  • 19 DiCarlo R, Meli R, Galdiero M, Nuzzo I, Bentivoglio C, Carratelli C R. Prolactin protection against lethal effects of Salmonella typhimurium. .  Life Science. 1993;  53 981-989
  • 20 Edwards C K, Ghiasuddin S M, Schepper J M, Yunger L M, Kelley K W. A newly defined property of somatotropin: priming of macrophages for production of superoxide anion.  Science. 1988;  239 769-771
  • 21 Fehr H G, Lotzerich H, Michna H. Influence of physical exercise on peritoneal macrophage functions: Histochemical and phagocytic studies.  Int J Spt Med. 1988;  9 77-81
  • 22 Fehr H G, Lotzerich H, Michna H. Human macrophage function and physical exercise: phagocytic and histochemical studies.  Eur J Appl Physiol. 1989;  58 613-617
  • 23 Forner M A, Collazos M E, Barriga C, De La Fuente M, Rodriguez A B, Ortega E. Effect of age on adherence and chemotaxis capacities of peritoneal macrophages. Influence of physical activity stress.  Mech Age Dev. 1994;  75 179-189
  • 24 Forner M A, Barriga C, Ortega E. Exercise-induced stimulation of murine macrophage phagocytosis may be mediated by thyroxine.  J Appl Physiol. 1996;  80 899-903
  • 25 Gabriel H, Urhausen A, Brechtel L, Muller H J, Kindermann W. Alterations of regular and mature monocytes are distinct, and dependent on intensity and duration of exercise.  Eur J Appl Physiol. 1994;  69 179-181
  • 26 Gagnerault M, Postel-Vinay M, Dardenne M. Expression of growth hormone receptors in murine lymphoid cells analyzed by flow cytofluorometry.  Endocrinology. 1996;  137 1719-1726
  • 27 Gala R R, Shevach E M. Identification by analytical flow cytometry of prolactin receptors on immunocompetent cell populations in the mouse.  Endocrinology. 1993;  133 1617-1623
  • 28 Gala R R, Shevach E M. Evidence for the release of a prolactin-like substance by mouse lymphocytes and macrophages.  Proc Soc Expt Biol Med. 1994;  205 12-18
  • 29 Guyton A C. Textbook of Medical Physiology (6th Ed). Philadelphia; W. B. Saunders 1981: 710-722
  • 30 Hagi K, Uno K, Inaba K, Muramatsu S. Augmenting effect of opioid peptides on murine macrophage activation.  J Neuroimmunol. 1994;  50 71-76
  • 31 Hagi K, Inaba K, Sakuta H, Muramatsu S. Enhancement of murine bone marrow macrophage differentiation by β-Endorphin.  Blood. 1995;  86 1316-1321
  • 32 Hogan M M, Vogel S N. Inhibition of macrophage tumoricidal activity by glucocorticoids.  J Immunol. 1988;  140 513-519
  • 33 Ichinose M, Asai M, Sawada M. β-endorphin enhances phagocytosis of latex particles in mouse peritoneal macrophages.  Scand J Immunol. 1995;  42 311-316
  • 34 Ignatowski T A, Spengler R N. Regulation of macrophage-derived tumor necrosis factor production by modification of adrenergic receptor sensitivity.  J Neuroimmunol. 1995;  61 61-70
  • 35 Inoue T, Saito H, Fukushima R, Fukatsu K, Lin M, Inaba T, Muto T. Growth hormone improves survival in a murine model of gram-negative sepsis.  Intensive Care Med. 1994;  20 S40
  • 36 Kelley K W. Immunologic roles of two metabolic hormones, growth hormone and insulin-like growth factor-I, in aged animals.  Nut Rev. 1995;  53 S95-S104
  • 37 Kleinert H, Euchenhofer C, Ihrig-Biedert I, Forstermann U. Glucocorticoids inhibit the induction of nitric oxide synthase II by down-regulating cytokine-induced activity of transcription factor nuclear factor-κB.  Mol Pharmacol. 1996;  49 15-21
  • 38 Kohut M L, Davis J M, Jackson D A, Hertler-Colbert L M, Strasner A, Essig D A, Pate R R, Ghaffar A, Mayer E P. The role of stress hormones in exercise-induced suppression of alveolar macrophage anti-viral function.  J Neuroimmunol. 1998;  81 193-200
  • 39 Kohut M L, Davis J M, Jackson D A, Jani P, Ghaffar A, Mayer E P, Essig D A. Exercise effects of IFN-β expression and viral replication in lung macrophages after HSV-1 infection.  Am J Physiol. 1998;  275 L1089-L1094
  • 40 Landmann R MA, Muller F B, Perini C, Wesp M, Erne P, Buchler F R. Changes of immunoregulatory cells induced by psychological and physical stress: relationship to plasma catecholamines.  Clin Expt Immunol. 1984;  58 127-135
  • 41 Liao W, Rudling M, Angelin B. Growth hormone potentiates the in vivo biological activities of endotoxin in the rat.  Eur J Clin Invest. 1996;  26 254-258
  • 42 Lu Q, Ceddia M A, Price E A, Woods J A. Chronic exercise increases macrophage-mediated anti-tumor cytolytic function in young and old mice.  Am J Physiol. 1999;  276 (2) R482-R489
  • 43 Madden K S, Sanders V M, Felten D L. Catecholamine influences and sympathetic neural modulation of immune responsiveness.  Annu Rev Pharmacol Toxicol. 1995;  35 417-448
  • 44 Mahan M P, Young M R. Immune parameters of untrained or exercise-trained rats after exhaustive exercise.  J Appl Physiol. 1989;  66 282-287
  • 45 Michna H. The human macrophage system: Activity and functional morphology.  Biblio Anatomica. 1988;  31 1-38
  • 46 Mills C D. M-1 and M-2 macrophages: who needs TH-1/TH-2?.  FASEB J. 1999;  13 (5, Part II) A647
  • 47 Murphy W J, Rui H, Longo D L. Effects of growth hormone and prolactin in immune development and regulation.  Life Science. 1995;  57 1-14
  • 48 Nagy E, Berczi I, Wren E, Asa S L, Kovacs K. Immunomodulation by bromocriptine.  Immunopharmacol. 1983;  6 231-243
  • 49 Northoff H, Enkel S, Weinstock C. Exercise, injury, and immune function.  Exerc Immunol Rev. 1995;  1 1-25
  • 50 Ortega E, Collazos M E, Barriga C, De la Fuente M. Stimulation of the phagocytic function in guinea pig peritoneal macrophages by physical activity stress.  Eur J Appl Physiol. 1992;  64 323-327
  • 51 Ortega E, Forner M A, Barriga C, De La Fuente M. Effect of age and of swimming-induced stress on the phagocytic capacity of peritoneal macrophages from mice.  Mech Age Dev. 1993;  70 53-63
  • 52 Ortega E, Rodriguez M J, Barriga C, Forner M A. Corticosterone, prolactin and thyroid hormones as hormonal mediators of the stimulated phagocytic capacity of peritoneal macrophages after high-intensity exercise.  Int J Spt Med. 1996;  17 149-155
  • 53 Ortega E, Forner M A, Barriga C. Exercise-induced stimulation of murine macrophage chemotaxis: role of corticosterone and prolactin as mediators.  J Physiol. 1997;  498 729-734
  • 54 Parry-Billings M, Blomstrand E, McAndrew N, Newsholme E A. A communicational link between skeletal muscle, brain, and cells of the immune system.  Int J Spt Med. 1990;  11 S122-S128
  • 55 Peterson P K, Sharp B M, Gekker G, Brummitt C, Keane W F. Opioid-mediated suppression of interferon-γ production by cultured peripheral blood mononuclear cells.  J Clin Invest. 1987;  80 824-831
  • 56 Rinehart J J, Wuest D, Ackerman G A. Corticosteroid alteration of human monocyte to macrophage differentiation.  J Immunol. 1982;  129 1436-1442
  • 57 Ruff M R, Wahl S M, Mergenhagen S, Pert C B. Chemotaxis of human monocytes.  Neuropeptides. 1985;  5 363-366
  • 58 Russo-Marie F. Macrophages and the glucocorticoids.  J Neuroimmunol. 1992;  40 281-286
  • 59 Saito H, Inoue T, Fukatsu K, Tsan L, Inaba T, Fukushima R, Muto T. Growth hormone and the immune response to bacterial infection.  Horm Res. 1996;  45 50-54
  • 60 Salkowski C A, Vogel S N. Lipopolysaccharide increases glucocorticoids receptor expression in murine macrophages.  J Immunol. 1992;  149 4041-4047
  • 61 Schaffner A. Therapeutic concentrations of glucocorticoids suppress the anti-microbial activity of human macrophages without impairing their responsiveness to γ-interferon.  J Clin Invest. 1985;  76 1755-1762
  • 62 Sharp B M, Keane W F, Suh J H, Gekker G, Tsukayama D, Peterson P K. Opioid peptides rapidly stimulate superoxide production by human polymorphonuclear leukocytes and macrophages.  Endocrinology. 1985;  117 793-795
  • 63 Sharp B M, Tsukayama D, Gekker G, Keane W F, Peterson P K. β-Endorphin simulates human polymorphonuclear leukocyte superoxide production via a stereoselective opiate receptor.  J Pharmacol Expt Ther. 1987;  242 579-582
  • 64 Sibinga N ES, Goldstein V. Opioid peptides and opioid receptors in cells of the immune system.  Annu Rev Immunol. 1988;  6 219-249
  • 65 Snyder D S, Unanue E R. Corticosteroids inhibit murine macrophage Ia expression and interleukin-1 production.  J Immunol. 1982;  129 1803-1807
  • 66 Spengler R N, Allen R M, Remick D G, Streiter R M, Kunkel S L. Stimulation of α-adrenergic receptor augments the production of macrophage-derived tumor necrosis factor.  J Immunol. 1990;  145 1430-1434
  • 67 Thompson J, Van Furth R. The effects of glucocorticosteroids on the proliferation and kinetics of promonocytes and monocytes of the bone marrow.  J Exp Med. 1973;  131 10-17
  • 68 Tosk J M, Grim J R, Kinback K M, Sale E J, Bozzetti L P, Will D. Modulation of chemiluminescence in a murine macrophage cell line by neuroendocrine hormones.  Int J Immunopharm. 1993;  15 615-620
  • 69 Tvede N, Kappel M, Klarlund K, Duhn S, Halkjaer-Kristensen J, Kjaer M, Galbo H, Pedersen B K. Evidence that the effect of bicycle exercise on blood mononuclear cell proliferative responses and subsets is mediated by epinephrine.  Int J Spt Med. 1994;  15 100-104
  • 70 Unanue E R. Macrophages, antigen-presenting cells, and the phenomena of antigen handling and presentation. In: Paul WE (Ed) Fundamental Immunology (3rd Ed). New York; Raven Press 1993: 111-144
  • 71 Van Epps D E, Saland L. β-Endorphin and met-enkephalin stimulate human peripheral blood mononuclear cell chemotaxis.  J Immunol. 1984;  132 3046-3053
  • 72 Van Furth R, Sluiter W. Distribution of blood monocytes between a marginating and a circulating pool.  J Exp Med. 1986;  163 474-479
  • 73 Van Furth R. Origin and turnover of monocyte and macrophages.  Curr Top Pathol. 1989;  79 125-140
  • 74 Warwick-Davies J, Lowrie D B, Cole P J. Growth hormone is a human macrophage activating factor. Priming of human monocytes for enhanced release of H2O2.  J Immunol. 1995;  154 1909-1918
  • 75 Watts C. Capture and processing of exogenous antigens for presentation on MHC molecules.  Annu Rev Immunol. 1997;  15 821-850
  • 76 Weigent D A, Blalock J E. Associations between the neuroendocrine and immune systems.  J Leuko Biol. 1995;  57 137-150
  • 77 Woods J A, Davis J M, Mayer E P, Ghaffar A, Pate R R. Exercise increases inflammatory macrophage anti-tumor cytotoxicity.  J Appl Physiol. 1993;  75 879-886
  • 78 Woods J A, Davis J M, Mayer E P, Ghaffar A, Pate R R. Effects of exercise on macrophage activation for anti-tumor cytotoxicity.  J Appl Physiol. 1994;  76 (5) 2177-2185
  • 79 Woods J A, Shahabi N S, Sharp B M. Characterization of a naloxone-resistant β-endorphin receptor on murine peritoneal macrophages.  Life Sciences. 1997;  60 (9) 573-586
  • 80 Woods J A, Ceddia M A, Kozak C, Wolters B W. Effects of exercixe on the macrophage MHC II response to inflammation.  Int J Spt Med. 1997;  18 483-488
  • 81 Woods J A, Davis J M, Smith J A, Nieman D C. Exercise and cellular innate immune function.  Med Sci Spt Exerc. 1999;  31 57-66
  • 82 Zanker B, Walz G, Wieder K J, Strom T B. Evidence that glucocorticoids block expression of the human interleukin-6 gene by accessory cells.  Transplantation. 1990;  49 183-188

Ph.D. J. A. Woods

University of Illinois

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