Exercise and cellular innate immune function.

Epidemiological evidence suggests a link between the intensity of exercise and infectious and neoplastic disease. One likely way by which exercise exerts its effect on cancer and infection is by altering the function of the immune system. Cells of the innate immune system (i.e., macrophage [Mphi], natural killer [NK] cell, and polymorphonuclear neutrophils [PMN]) are first-line defenders against cancer and infectious disease by nature of their phagocytic, cytolytic, and antimicrobial properties. The purpose of this review is to define the role of cells of the innate immune system (i.e., Mphi, PMN, and NK cells) in infection and cancer, present current information regarding the effects of acute and chronic exercise on the quantification and functional activities of these cells, and briefly to discuss potential mechanisms as to how exercise affects these cells and describe how these changes may potentially affect susceptibility to infection and cancer. The effects of exercise on the number, functions, and characteristics of cells of the innate immune system are complex and are dependent several factors, including 1) the cell function or characteristic being analyzed; 2) the intensity, duration and chronicity of exercise; 3) the timing of measurement in relation to the exercise bout; 4) the dose and type of immunomodulator used to stimulate the cell in vitro or in vivo; and 5) the site of cellular origin. Further studies are needed to determine whether the exercise-induced changes in immune function alter incidence or progression of disease. Likewise, the mechanisms as to how exercise alters innate immune function are as yet unresolved.

[1]  S. Arkins,et al.  Interferon‐γ‐induced priming for secretion of superoxide anion and tumor necrosis factor‐α declines in macrophages from aged rats , 1990, The FASEB Journal.

[2]  A. Kharazmi,et al.  Indometacin In Vitro and In Vivo Abolishes Post-Exercise Suppression of Natural Killer Cell Activity in Peripheral Blood , 1990, International journal of sports medicine.

[3]  B. Pedersen,et al.  Natural Killer Cell Activity in Peripheral Blood of Highly Trained and Untrained Persons , 1989, International journal of sports medicine.

[4]  J. Davis,et al.  Carbohydrate affects natural killer cell redistribution but not activity after running. , 1997, Medicine and science in sports and exercise.

[5]  M. Young,et al.  Immune parameters of untrained or exercise-trained rats after exhaustive exercise. , 1989, Journal of applied physiology.

[6]  C. Barriga,et al.  Corticosterone, Prolactin and Thyroid Hormones as Hormonal Mediators of the Stimulated Phagocytic Capacity of Peritoneal Macrophages After High-Intensity Exercise , 1996, International journal of sports medicine.

[7]  Z. Reiter Interferon--a major regulator of natural killer cell-mediated cytotoxicity. , 1993, Journal of interferon research.

[8]  R. Pate,et al.  Exercise increases inflammatory macrophage antitumor cytotoxicity. , 1993, Journal of applied physiology.

[9]  A. Heidland,et al.  Activation of leukocytes during prolonged physical exercise. , 1988, Advances in experimental medicine and biology.

[10]  Y. Kurokawa,et al.  Triathlon competition induced a transient immunosuppressive change in the peripheral blood of athletes. , 1993, The Journal of sports medicine and physical fitness.

[11]  M. Kjaer,et al.  Evidence that the effect of physical exercise on NK cell activity is mediated by epinephrine. , 1991, Journal of applied physiology.

[12]  D. Pyne,et al.  Exercise, training, and neutrophil function. , 1997, Exercise immunology review.

[13]  P. Shek,et al.  Strenuous Exercise and Immunological Changes , 1995 .

[14]  G. Bagby,et al.  Prior exercise suppresses the plasma tumor necrosis factor response to bacterial lipopolysaccharide. , 1994, Journal of applied physiology.

[15]  R. Shephard,et al.  Acute Exercise and Immune Function , 1992 .

[16]  B. Sternfeld,et al.  Cancer and the protective effect of physical activity: the epidemiological evidence. , 1992, Medicine and science in sports and exercise.

[17]  B. Dufaux,et al.  Plasma elastase-alpha 1-antitrypsin, neopterin, tumor necrosis factor, and soluble interleukin-2 receptor after prolonged exercise. , 1989, International journal of sports medicine.

[18]  T. Hamilton,et al.  The cell biology of macrophage activation. , 1984, Annual review of immunology.

[19]  A. van As,et al.  The effect of exercise on secretory and natural immunity. , 1987, Advances in experimental medicine and biology.

[20]  B. Macneil,et al.  Chronic exercise enhances in vivo and in vitro cytotoxic mechanisms of natural immunity in mice. , 1993, Journal of applied physiology.

[21]  R. H. Bonneau Stress-Induced Effects on Integral Immune Components Involved in Herpes Simplex Virus (HSV)-Specific Memory Cytotoxic T Lymphocyte Activation , 1996, Brain, Behavior, and Immunity.

[22]  J A Smith Guidelines, standards, and perspectives in exercise immunology. , 1995, Medicine and science in sports and exercise.

[23]  I. Rubinstein,et al.  Neutrophil Chemotactic Activity is Increased in Nasal Secretions of Long-Distance Runners , 1996, International journal of sports medicine.

[24]  H. Ullum,et al.  Bicycle exercise enhances plasma IL-6 but does not change IL-1 alpha, IL-1 beta, IL-6, or TNF-alpha pre-mRNA in BMNC. , 1994, Journal of applied physiology.

[25]  H. Ullum,et al.  NK cell response to physical activity: possible mechanisms of action. , 1994, Medicine and science in sports and exercise.

[26]  C. Heijnen,et al.  β2‐Adrenergic stimulation causes detachment of natural killer cells from cultured endothelium , 1993, European journal of immunology.

[27]  Moderate exercise training and natural killer cell cytotoxic activity in breast cancer patients. , 1995, International journal of sports medicine.

[28]  N. Christensen,et al.  Natural killer cell activity during cortisol and adrenaline infusion in healthy volunteers , 1987, European journal of clinical investigation.

[29]  S. Gaffin,et al.  Strenuous exercise causes systemic endotoxemia. , 1988, Journal of applied physiology.

[30]  R. Telford,et al.  Exercise, Training and Neutrophil Microbicidal Activity , 1990, International journal of sports medicine.

[31]  C. Barriga,et al.  Exercise-induced stimulation of murine macrophage phagocytosis may be mediated by thyroxine. , 1996, Journal of applied physiology.

[32]  G. Trinchieri Natural killer cells wear different hats: effector cells of innate resistance and regulatory cells of adaptive immunity and of hematopoiesis. , 1995, Seminars in immunology.

[33]  T. Noakes,et al.  Vitamin C supplementation reduces the incidence of postrace symptoms of upper-respiratory-tract infection in ultramarathon runners. , 1993, The American journal of clinical nutrition.

[34]  R. Pate,et al.  Effects of exercise on macrophage activation for antitumor cytotoxicity. , 1994, Journal of applied physiology.

[35]  J. Davis,et al.  Effects of high- vs moderate-intensity exercise on natural killer cell activity. , 1993, Medicine and science in sports and exercise.

[36]  R. Gougeon,et al.  Circulating mononuclear cell numbers and function during intense exercise and recovery. , 1991, Journal of applied physiology.

[37]  R. Day,et al.  Natural killer cytotoxicity in the diagnosis of immune dysfunction: Criteria for a reproducible assay , 1990, Journal of clinical laboratory analysis.

[38]  B. Pedersen,et al.  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. , 1993, International journal of sports medicine.

[39]  E. Bluman,et al.  Human natural killer cells produce abundant macrophage inflammatory protein-1 alpha in response to monocyte-derived cytokines. , 1996, The Journal of clinical investigation.

[40]  D. Nieman,et al.  The Effects of Moderate Exercise Training on Natural Killer Cells and Acute Upper Respiratory Tract Infections , 1990, International journal of sports medicine.

[41]  N. York,et al.  The Influence of Physical Exercise on Peritoneal Macrophage Functions: Histochemical and Phagocytic Studies , 1988, International journal of sports medicine.

[42]  L. Hoffman‐Goetz Exercise, natural immunity, and tumor metastasis. , 1994, Medicine and science in sports and exercise.

[43]  D. Nieman,et al.  The effect of long endurance running on natural killer cells in marathoners. , 1990, Medicine and science in sports and exercise.

[44]  J. Trapani,et al.  Target cell apoptosis induced by cytotoxic T cells and natural killer cells involves synergy between the pore-forming protein, perforin, and the serine protease, granzyme B. , 1995, Australian and New Zealand journal of medicine.

[45]  D. Newman Meals Services for Old People , 1953 .

[46]  J. Davis,et al.  Exercise, alveolar macrophage function, and susceptibility to respiratory infection. , 1997, Journal of applied physiology.

[47]  T. Whiteside,et al.  Role of human natural killer cells in health and disease , 1994, Clinical and diagnostic laboratory immunology.

[48]  J. Davis,et al.  The role of stress hormones in exercise-induced suppression of alveolar macrophage antiviral function , 1998, Journal of Neuroimmunology.

[49]  H Tchórzewski,et al.  Effect of physical exercise on some parameters of immunity in conditioned sportsmen. , 1987, International journal of sports medicine.

[50]  M. De la Fuente,et al.  Changes in the phagocytic function of peritoneal macrophages from old mice after strenuous physical exercise. , 1990, Comparative immunology, microbiology and infectious diseases.

[51]  J. Davis,et al.  Exercise, monocyte/macrophage function, and cancer. , 1994, Medicine and science in sports and exercise.

[52]  Z. Cohn Activation of mononuclear phagocytes: fact, fancy, and future. , 1978, Journal of immunology.

[53]  N. York,et al.  A Communicational Link Between Skeletal Muscle, Brain, and Cells of the Immune System , 1990, International journal of sports medicine.

[54]  M. De la Fuente,et al.  Phagocytic Function of Blood Neutrophils in Sedentary Young People after Physical Exercise , 1991, International journal of sports medicine.

[55]  H. Northoff,et al.  Effect of exhaustive exercise stress on the cytokine response. , 1997, Medicine and science in sports and exercise.

[56]  J. D'Orazio,et al.  Human natural killer (NK) cells present staphylococcal enterotoxin B (SEB) to T lymphocytes , 1996, Clinical and experimental immunology.

[57]  V. Hack,et al.  PMN cell counts and phagocytic activity of highly trained athletes depend on training period. , 1994, Journal of applied physiology.

[58]  U. Dahlgren,et al.  Voluntary chronic exercise augments in vivo natural immunity in rats. , 1996, Journal of applied physiology.

[59]  B. Pedersen,et al.  Effect of 8 wk of bicycle training on the immune system of patients with rheumatoid arthritis. , 1993, Journal of applied physiology.

[60]  D. Pyne,et al.  Effects of an intensive 12-wk training program by elite swimmers on neutrophil oxidative activity. , 1995, Medicine and science in sports and exercise.

[61]  K. Nakanishi,et al.  Effect of exercise on endotoxin shock with special reference to changes in concentration of cytokines. , 1995, The Japanese journal of physiology.

[62]  C. Barriga,et al.  Exercise‐induced stimulation of murine macrophage chemotaxis: role of corticosterone and prolactin as mediators. , 1997, The Journal of physiology.

[63]  T. Whiteside,et al.  The role of natural killer cells in immune surveillance of cancer. , 1995, Current opinion in immunology.

[64]  R. Pate,et al.  Effects of exercise on the immune response to cancer. , 1992, Medicine and science in sports and exercise.

[65]  John A. Smith Neutrophils, host defense, and inflammation: a double‐edged sword , 1994, Journal of leukocyte biology.

[66]  W. Wolters,et al.  Effects of Exercise on the Macrophage MHC II Response to Inflammation , 1997, International journal of sports medicine.

[67]  C. Barriga,et al.  Effect of age and of swimming-induced stress on the phagocytic capacity of peritoneal macrophages from mice , 1993, Mechanisms of Ageing and Development.

[68]  A. Yamauchi,et al.  Target-induced death by apoptosis in human lymphokine-activated natural killer cells. , 1996, Blood.

[69]  R. Shephard,et al.  Cancer, immune function, and physical activity. , 1995, Canadian journal of applied physiology = Revue canadienne de physiologie appliquee.

[70]  N. Pavlidis,et al.  Stress‐induced Impairment of Macrophage Tumoricidal Function , 1980, Psychosomatic medicine.

[71]  M. Baker,et al.  Granulocyte activation induced by intense interval running , 1993, Journal of leukocyte biology.

[72]  R. Khatib,et al.  Modification of exercise-aggravated coxsackievirus B3 murine myocarditis by T lymphocyte suppression in an inbred model. , 1990, The Journal of laboratory and clinical medicine.

[73]  R. Day,et al.  Calculation of lytic units for the expression of cell-mediated cytotoxicity. , 1992, Journal of immunological methods.

[74]  L. Saravolatz,et al.  Selective inhibitory effects of stress hormones on natural killer (NK) cell activity of lymphocytes from AIDS patients. , 1995, Immunological investigations.

[75]  E. Thorsby,et al.  Influence of in Vivo Hydrocortisone on Some Human Blood Lymphocyte Subpopulations , 1981, Scandinavian journal of immunology.

[76]  W. Kindermann,et al.  Suppressed PMA-induced oxidative burst and unimpaired phagocytosis of circulating granulocytes one week after a long endurance exercise. , 1994, International journal of sports medicine.

[77]  Julie Brittenden,et al.  Natural killer cells and cancer , 1996, Cancer.

[78]  M. Dale,et al.  The Leucocytosis of Exercise , 1988 .

[79]  J. Suttles,et al.  Immune function in marathon runners versus sedentary controls. , 1995, Medicine and science in sports and exercise.

[80]  B. Pedersen,et al.  Can you exercise to make your immune system fitter? , 1996, Immunology today.

[81]  D A Henson,et al.  Physical activity and immune function in elderly women. , 1993, Medicine and science in sports and exercise.

[82]  V. Riley Psychoneuroendocrine influences on immunocompetence and neoplasia. , 1981, Science.

[83]  M. Kluger,et al.  Human neutrophil hydrogen peroxide generation following physical exercise. , 1990, The Journal of sports medicine and physical fitness.

[84]  R. Shephard,et al.  Physical activity and immune senescence in men. , 1995, Medicine and science in sports and exercise.

[85]  G. Lippi,et al.  Changes in several neutrophil functions in basketball players before, during and after the sports season. , 1995, International journal of sports medicine.

[86]  G. Müns,et al.  Effect of Long-Distance Running on Polymorphonuclear Neutrophil Phagocytic Function of the Upper Airways , 1994, International journal of sports medicine.

[87]  C. Barriga,et al.  Effect of age on adherence and chemotaxis capacities of peritoneal macrophages. Influence of physical activity stress , 1994, Mechanisms of Ageing and Development.

[88]  P. Parham,et al.  The enigma of the natural killer cell , 1995, Nature.

[89]  S. Jawahar,et al.  Natural killer (NK) cell deficiency associated with an epitope‐deficient Fc receptor type IIIA (CD16‐II) , 1996, Clinical and experimental immunology.

[90]  J. Davis,et al.  Indomethacin does not alter natural killer cell response to 2.5 h of running. , 1995, Journal of applied physiology.

[91]  D. Nieman,et al.  Infectious episodes in runners before and after the Los Angeles Marathon. , 1990, The Journal of sports medicine and physical fitness.

[92]  H. Appell,et al.  Potentiation of Cytostatic But Not Cytolytic Activity of Murine Macrophages After Running Stress* , 1990, International journal of sports medicine.