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Beta-blockers, exercise, and the immune system in men with coronary artery disease.

PURPOSE: The purpose of the present study was to examine the effect of aerobic exercise training on the immune system in coronary artery disease patients treated with beta-blockers. METHODS: Twenty-five patients (46.1 +/- 2 yr) treated with atenolol, a beta-blocker agent, for 3 months before exercising were divided randomly into two groups: 15 underwent an aerobic exercise training program for 12 wk at 65-70% of their work capacity, whereas the other 10 patients served as controls. RESULTS: After training, levels of CD4 and CD8 cells were significantly (P < 0.05) higher and concomitantly the CD4/CD8 ratio decreased significantly (P < 0.05) in the exercising group compared with the control group. CONCLUSIONS: Data suggest that coronary artery disease patients exercising aerobically at 65-70% of their work capacity gain a statistically significant higher lymphocyte T cell function as compared with their untrained counterparts.

Adrenergic beta-Antagonists↗

Decreased salivary immunoglobulins after intense interval exercise before and after training.

Endurance athletes have been shown to suffer a high incidence of upper respiratory tract infection (URTI). Previous studies have shown that concentration and flow rate of secretory immunoglobulin A (IgA), the major effector of host resistance to URTI, decrease after intense endurance exercise. The purpose of this study was to determine whether salivary IgA concentration and flow rate decrease after brief intense interval exercise, and whether the response to exercise changes with training. Twelve male subjects performed five 60-s bouts of supramaximal interval exercise at 0.075 g.kg-1 body mass on a cycle ergometer; each bout was separated by 5-min rest. Subjects then trained for 8 wk by performing the same interval exercise protocol three times per week. Timed, whole unstimulated saliva samples were obtained before and after the interval exercise protocol, before and after training. Salivary IgA, IgG, and IgM concentrations were measured by ELISA and flow rates calculated. IgA and IgM concentrations relative to total protein decreased after each exercise session; IgG concentration relative to total protein did not change after exercise. IgA, IgM, and IgG flow rates decreased 50-65% after interval exercise. There was no effect of training on any immune parameter measured, although total work performed in the five 60-s bouts increased after training. These data show that the output of salivary IgA and IgM decrease after brief supramaximal interval exercise, and that the decreased output is due, at least partially, to the decrease in saliva flow. In addition, there appears to be a specific effect of intense exercise on IgA concentration greater than that due to decreased saliva flow alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Anaerobic exercise causes transient changes in leukocyte subsets and IL-2R expression.

There is evidence that the stress of intense athletic competition and training depresses cellular immunity and predisposes athletes to increased infection. This paper reports changes in circulating leukocyte subsets of trained (group I: VO2max = 67.2 +/- 5.4 ml.kg-1min-1; age = 22.0 +/- 6.2 yr) and untrained (group II: VO2max = 55.0 +/- 4.9 ml.kg-1min-1; age = 21.4 +/- 2.0 yr) males following 1 min of bicycle ergometry at maximum effort. Significant post-exercise increases in concentrations of total leukocytes, monocytes, lymphocytes, CD3+, CD4+, CD8+ lymphocytes were observed in both groups (all P < 0.01). The CD4/CD8 ratio decreased significantly (P < 0.01) but the granulocyte concentration was not altered (P > 0.05). Despite groups I and II not differing in either peak power or total work performed during the exercise test (P > 0.05), group II had a significantly greater concentration and percentage of CD8+ lymphocytes immediately after exercise (P < 0.01). All of the early changes were transient, with normalization occurring within 1 h. Only trained subjects showed a significant decrease in the percentage of CD25+ lymphocytes following PHA stimulation of whole blood obtained 6 h post-exercise. Alterations in leukocyte subpopulations found in response to predominantly anaerobic exercise appear to be associated with a significant, but possibly transient, alteration in the mitogenic responsiveness of lymphocytes that is restricted to aerobically trained subjects.

Adolescent↗

Plasma zinc and immune markers in runners in response to a moderate increase in training volume.

Changes in plasma zinc concentration and markers of immune function were examined in a group of 10 male runners (n = 10) following a moderate increase in training over four weeks. Seven sedentary males acted as controls. Fasting blood samples were taken at rest, before (T0) and after (T4) four weeks of increased (+ 16 %) training and after two weeks of reduced (-31 %) training (T6). Blood was analysed for plasma zinc concentration, differential leucocyte counts, lymphocyte subpopulations and lymphocyte proliferation using incorporation of 3H-thymidine. The runners increased their training volume by 16 % over the four weeks. When compared with the nonathletes, the runners had lower concentrations of plasma zinc (p = 0.012), CD3 + (p = 0.042) and CD19 + lymphocytes (p = 0.010) over the four weeks. Lymphocyte proliferation in response to Concanavalin A stimulation was greater in the runners (p = 0.0090). Plasma zinc concentration and immune markers remained constant during the study. Plasma zinc concentration correlated with total leucocyte counts in the athletes at T6 (r = -0.72, p < 0.05) and with Pokeweed mitogen stimulation in the nonathletes at T6 (r = -0.92, p < 0.05). Therefore, athletes are unlikely to benefit from zinc supplementation during periods of moderately increased training volume.

Adaptation, Physiological↗

Improving immunization coverage, a comparison between traditional MCH teams and MCH teams plus aid post orderlies.

Aid post orderlies in one district of the Southern Highlands Province were trained to give immunizations to children as part of the Expanded Programme on Immunization. The performance of the aid post orderlies (APOs) as immunizers is compared with that of the traditional maternal and child health (MCH) team. Also the results of the combined efforts of the APOs and MCH sisters in this pilot district are compared with those in a control district. The joint APO-MCH effort was more successful than the traditional approach in reaching national immunization targets.

Allied Health Personnel↗

Issues in AIDS training for substance abuse workers.

Workers in drug treatment programs need specialized training concerning acquired immune deficiency syndrome (AIDS) to meet the demands of their expanding roles. Initially, the treatment community failed to anticipate training needs fully, but now, comprehensive and systematic AIDS training programs must be developed. This article discusses the five steps in developing and implementing such programs: (a) assessment and information gathering, (b) curriculum development, (c) training of instructors, (d) training delivery, and (e) evaluation.

Acquired Immunodeficiency Syndrome↗

Future directions in exercise and immunology: regulation and integration.

Although it is difficult to predict future directions in a rapidly expanding field such as exercise immunology, recently published research along with that presented at this Symposium allow us to ask some key questions which may point to new directions: 1) Are athletes immunocompromised? Athletes are not clinically immunodeficient, yet endurance athletes are at increased risk of illness. Long-term prospective studies are needed to understand the relationship between infection, training variables and immune parameters. 2) Is downregulation of nonspecific immunity beneficial or harmful? In athletes, neutrophils appear to be downregulated, and this may alter resistance to illness. Alternatively, neutrophils are mediators of tissue damage during inflammation. Downregulation of neutrophil function may be protective by limiting chronic inflammation. In athletes, mild immunosuppression may reflect a compromise between the body's attempts to limit inflammation while maintaining immune function. 3) What mediates communication between events in skeletal muscle and the immune system? Leukocyte mobility is affected by metabolic and mechanical factors during exercise. Exercise increases cytokine levels in damaged skeletal muscle and expression of adhesion molecules. Future work is likely to focus on the role of cytokines and adhesion molecules in mediating exercise-induced changes in leukocyte mobility. 4) Can exercise training provide a "countermeasure" against immunosuppressive events? Moderate exercise training may have a role in stimulating the immune system during certain diseases (e.g., HIV-infection), immune dysfunction (e.g., chronic fatigue syndrome) or reduced responsiveness (e.g. aging, spaceflight). It is also likely that future study will apply molecular biology techniques to further identify mechanisms by which exercise influences immune function.

Animals↗

Regular moderate exercise training prevents decrease of CD4+ T-lymphocytes induced by a single bout of strenuous exercise in mice.

The biphasic effects of exercise training on the immune system have been studied extensively and represented by the well-known J-shaped curve with respect to training intensity. However, the relationship and interactions between "beneficial" exercise training and "harmful" strenuous exercise have not been researched. This study was designed to determine whether regular moderate exercise training could affect the changes of percentage of T-lymphocytes induced by a single bout of strenuous exercise. A protocol to run uphill on a 10 degrees tilted treadmill for 4 weeks was employed as moderate exercise training in mice, while a sedentary control group of mice was exposed to the same handling stress without training. The trained and untrained mice were then exposed to a single bout of strenuous exercise until exhaustion. Total leukocytes were collected from spleen and peripheral blood at 0 hr, 3 hrs, and 24 hrs postexhaustion, as well as from the control groups. Flow cytometric analyses were conducted to determine the percentages of selected leukocyte populations. It was demonstrated that moderate exercise training prevented the decrease of CD4+ but stimulated the increase of CD25+ CD8+ T-lymphocytes induced by a single bout of strenuous exercise, indicating an adaptive response that can affect changes of leukocyte subpopulations.

Animals↗

Age-related immunosenescence in Fischer 344 rats: influence of exercise training.

The present investigation examined the extent to which 15 wk of endurance training could influence immune function in young, middle-aged, and older animals. Forty-eight male Fischer 344 rats were divided into trained and untrained groups. Training consisted of treadmill running at 75% maximal running capacity for 1 h/day, 5 days/wk, for 15 wk. Animals were killed at 8, 17, and 27 mo, at which time splenocytes were isolated. The capacity for lymphocyte proliferation in response to mitogen (concanavalin A, ConA), interleukin-2 (IL-2) production, and cytolytic activity against YAC-1 target cells was determined. ConA-induced proliferation declined significantly with age. Training suppressed the proliferative response in the young (-41%) and middle-aged animals (-27%) compared with the age-matched controls; however, training improved this response (+58%) in the older group. IL-2 production followed a pattern similar to that for mitogen-induced proliferation, such that production declined with age and was reduced with training in young and middle-aged animals but was significantly more improved in the older animals than in age-matched controls. The ability to lyse target cells, measured as percent cytotoxicity, declined steadily with advancing age at all effector-to-target cell ratios tested: 52, 14, and -16% for 8-, 17-, and 27-mo-old rats, respectively. It was concluded that the capacity for ConA-induced splenocyte proliferation, IL-2 production, and cytolytic activity declines significantly with advancing age. Furthermore, 15 wk of endurance training suppressed proliferation and IL-2 production in young animals but improved these responses in older animals. Training had no effect on cytolytic activity.

Aging↗

Overtraining increases the susceptibility to infection.

Recent research studies and other evidence suggest that although moderate exercise is good for the immune system, the demanding training programs of many top athletes may suppress the immune system and thereby increase susceptibility to infections. A number of top athletes have suffered from unusual infections normally associated with immune deficiency, and immune abnormalities have been demonstrated in resting samples from top athletes. Studies from several exercise laboratories have shown that after a single exhausting exercise session there is temporary immune depression, with marked changes in numbers and functional capacities of lymphocytes. These changes, which last for up to several hours, are seen in athletes and untrained individuals. In several studies in the United States, students who were very active in sports have been shown to be more susceptible to infections than their less active colleagues. Exercising hard during the incubation phase of an infection can increase the severity of the illness. This article examines the evidence, discusses possible mechanisms, and considers the implications.

Disease Susceptibility↗

The gastrointestinal system--an essential target organ of the athlete's health and physical performance.

An athlete's ability to reach maximum performance is a direct result of physical and muscular performance, muscular and systemic stress tolerance, control and regulation of immune function, and adaptation to physical stress. In this complex sense, the gastrointestinal (GI) tract is also part of the system that controls and regulates adaptation and regeneration of the athlete. A well-balanced GI immune system and an optimized immune competence may protect the athlete from harmful pathogens; it may also protect against dietary as well as inhaled antigens. However, under conditions of mechanical and biochemical stress, the integrity of the GI mucosal block, particularly the epithelial hood, can be damaged, leading to a pathological uptake of toxic or immunogenic substrates. This may occur in endurance athletes, since gut symptomatology, nausea, vomiting, pain, bloating, diarrhea, cramping, and bleeding can be observed in up to half of all participants in endurance events. In addition, composition of stool and fecal microflora in endurance athletes has shown that there may be a specific need for nutritional support for mucosal immunity in highly trained but chronically stressed athletes. Proper diet during training and competition is a significant factor in guarding against GI symptoms and exercise-induced gastrointestinal side effects that may compromise immune competence and physical performance. The present review presents some important suggestions on the possible role of the GI tract in human performance and stress tolerance, and offers new insights about the influence of food quality on the immune system of the gut.

Digestive System↗

Effects of a long-term training program of increasing intensity on the immune function of indoor Olympic cyclists.

We have studied, on blood samples, the level of immunocompetence (concentration of immune cells, phagocytic process of polymorphonuclear neutrophils, proliferative response of lymphocytes to mitogens), the ascorbic acid content of such immunocompetent cells and the "stress hormone" status (cortisol, ACTH and beta-endorphin) of 10 cyclists, members of the Spanish Indoor Olympic Team and participants in the Olympic Games of Barcelona '92. The study was performed twice during their training for such an event: during the third year of the program (February, 1991) and immediately before the Games (June, 1992). As regards the phagocytic process of neutrophils, we studied the different steps of this process: adherence to endothelium, directed mobility or chemotaxis, ingestion of latex beads and superoxide anion production measured by the nitroblue tetrazolium (NBT) reduction test. We observed a statistically significant increase in chemotaxis and NBT reduction activity just before the Games as compared to the third year of the program, whereas variations were not found in the other parameters. The values of the proliferative capacity of lymphocytes were slightly higher in June '92 than in February '91, but no statistically significant differences were found. The ascorbic acid content decreased strikingly (especially in lymphocytes) immediately before the Games. Regarding the stress hormones and neuropeptides (cortisol, ACTH and beta-endorphin), we observed an increase in serum ACTH and beta-endorphin levels in the last determination (June '92) in comparison to the first one (February '91). These results suggest that, at the end of a long-term training program. no immunosuppression occurs, although an important increase in the concentration of stress hormones (ACTH and beta-endorphin) is found. This is probably caused by the psychological stress associated to the participation in such an important event as the Olympic Games.

Adrenocorticotropic Hormone↗

Qi-training enhances respiratory burst function and adhesive capacity of neutrophils in young adults: a preliminary study.

The main objective of this study is to examine the effect of Qi-training on the immune system, especially neutrophil bactericidal function. Nine healthy male subjects were studied for the effects of one bout of ChunDoSunBup (CDSB) Qi-training on superoxide (O2- production and adhesion capacity of neutrophils at times immediately after (Post I) and 2 hours after the Qi-training (Post II). The Qi-training enhanced O2- production, reaction velocity and neutrophil adhesion capacity and there were significant differences at Post I compared to before Qi-training (Pre). In addition, the number of white blood cells (WBC), monocytes and lymphocytes were changed significantly through Qi-training.Therefore, it seems that CDSB Qi-training may increase the resistance of trained individuals against common infection and inflammation.

Adult↗

Moderate exercise improves antibody response to influenza immunization in older adults.

Influenza vaccine efficacy is reduced among adults over age 65 and a significant number of vaccinated elderly may remain susceptible to influenza virus infection. The effect of moderate exercise training on the immune response to influenza immunization was evaluated in this study. Twenty-seven adults >or=age 64 were assigned to an exercise group (n= 14) or a control group (n = 13). The subjects exercised at 65-75% heart rate reserve (HRR), 25-30 min, 3 days per week, for 10 months. Controls did not change activity. Subjects were immunized with trivalent influenza vaccine before and after the exercise intervention. After the exercise intervention, exercisers exhibited a greater mean fold increase (MFI) in antibody titer to influenza A/New Caledonia/20/99 (H1N1) and A/Panama/2007/99 (H3N2) than controls, and a greater Granzyme B activity to A/Panama/2007/99 than controls. These findings suggest that exercise may enhance the mean fold increase in antibody titer in response to influenza immunization if the influenza antigen was contained in the previous year's vaccine.

Adult↗

Relationships between physiological and psychological stress and salivary immunoglobulin A among young female gymnasts.

We investigated whether psychological and physical stress induced by training or competition influence the secretory immune system among 12 highly trained young female gymnasts. Salivary levels of secretory IgA and cortisol responses to gymnastic training session or competition were assessed a total of 10 times, immediately before and after two training sessions which had different intensities and just before and after a major competition. These parameters were also measured on two non-training days. The Brunel Mood Scale was also used to assess the gymnasts's overall mood on each test day. IgA:Protein ratio was calculated. Significant decreases in this ratio were found after each exercise session, related to the physiological and psychological stress induced by exercise. Over the 5-mo. training period the presession IgA:Protein ratios were unchanged. Gymnasts registered any episodes of upper respiratory tract infection. Bouts of exercise induce transitory effects on the immune system in relation to the workload and the stress induced by the exercise without any relation to increased susceptibility to illness in children.

Body Mass Index↗

Effect of immune system imagery on secretory IgA.

This study was an investigation of the effects of physiologically-oriented mental imagery on immune functioning. College students with normal medical histories were randomly selected to one of three groups. Subjects in Group 1 participated in short educational training on the production of secretory immunoglobulin A. They were then tested on salivary IgA, skin temperature, and the Profile of Mood States (POMS) before and after listening to a 17-minute tape of imagery instructions with specially composed background "entrainment" music designed to enhance imagery. Subjects in Group 2 (placebo controls) listened to the same music but received nor formal training on the immune system. Group 3 acted as a control and subjects were tested before and after 17 minutes of no activity. Treatment groups listened to their tapes at home on a bi-daily basis for six weeks. All groups were again tested at Weeks 3 and 6. Secretory IgA was analyzed using standard radial immunodiffusion techniques. Repeated measures analyses of variance with planned orthogonal contrasts were used to evaluate the data. Significant overall increases (p less than 0.05) were found between pre- and posttests for all three trials. Groups 1 and 2 combined (treatment groups) yielded significantly greater increases in sIgA over Group 3 (control) for all three trials. Group 1 (imagery) was significantly higher than Group 2 (music) in antibody production for Trials 2 and 3. Symptomatology, recorded by subjects at Weeks 3 and 6, was significantly lower for three symptoms (rapid heartbeat, breathing difficulty, and jaw clenching), favoring both treatment groups over the control group.

Humans↗

Observations on the proposed relationship between infection burden and early malignancy in developing countries (e.g., India).

Sastry and Parikh [Med. Hypotheses 60(4) (2003) 573] have recently sought an explanation for the fact that the occurrence of a particular cancer in populations in a developing country such as India takes place at a younger age (about one decade) than in populations in Western countries. They have hypothesized that a higher infectious burden in India gives rise to repeated cell divisions leading to early senescence of immune cells, and, thence their reduced ability for immune surveillance against cancer, resulting in earlier onset of cancer. The analysis presented here points out to some difficulties with this interpretation, both on empirical and theoretical grounds. The reduced surveillance ability, caused by higher infectious burden, of the immune cells postulated by Sastry and Parikh [loc. cit.] would also mean that populations in India should suffer higher incidence of cancer, as compared to people in Western countries; the empirical data show that, in fact, quite the opposite is true - in the present communication shows that for many common cancers, typical cities in India show the lowest incidence. Theoretically, it is postulated here that repeated heavy infections in India, in fact, challenge the immune system, particularly the adaptive immune system and create an immunological memory: this trains and strengthens the immune system against the future battles. Also it is shown that the shortening of the telomeric cap by repeated cell divisions caused by heavy infectious attacks, as argued by Sastry and Parikh [loc. cit.], is not the cause of earlier onset of cancers among Indians; in fact, when telomeric caps become shortened to a critical point, a danger signal is generated arresting the cell cycle - thus, it provides a fundamental mechanism for ordering the cell to cease proliferation. It is suggested that the root of occurrence of cancers at an earlier age in India perhaps lies in the accumulation of mutations at an earlier age among Indians who do develop cancers; the factors responsible for these accelerated mutations are not clear at the present time and need further investigation.

Age Distribution↗

Exercise and training: influences on cytotoxicity, interleukin-1, interleukin-2 and receptor structures.

Exercise responses are discussed with particular reference to the functional system involving interleukin-1, interleukin 2 and cytotoxicity. Prolonged endurance exercise causes an increase in plasma levels of interleukin-1, possibly as a response to muscle injuries, but plasma interleukin-2 levels generally fall. The latter change probably reflects stronger binding, consequent upon increased expression of p70-75 receptors for IL-2, and changes in the distribution or activity of target cells; IL-1 secretion may enhance the responsiveness of peripheral blood mononuclear cells, but prostaglandin secretion decreases their IL-2 production. Moderate exercise increases the cytolytic action of NK cells, but there is a prolonged fall of cytolytic activity after exhausting or psychologically stressful exercise; again these responses probably reflect altered IL-2 levels or receptor expression. Appropriately graded training reduces the adverse immune reactions associated with challenging exercise. Cross-sectional comparison and training experiments both show an increased expression of p70-75 IL-2 receptors on the NK cells of active individuals. Moreover, moderate training reduces the exercise-induced suppression of IL-2 production. However, training that is pursued to the level of staleness, nutrient deficiency or muscle damage has a negative impact upon both the production of interleukins and the leukocyte response. Coaches must thus gauge training programs to optimize not only physiological function but also immune responses.

Cytotoxicity, Immunologic↗