Special feature for the Olympics: effects of exercise on the immune system: exercise and cytokines

Strenuous exercise induces increased levels in a number of pro-inflammatory and anti-inflammatory cytokines, naturally occurring cytokine inhibitors and chemokines. Thus, increased plasma levels of TNF-alpha, IL-1, IL-6, IL-1 receptor antagonist, TNF receptors, IL-10, IL-8 and macrophage inflammatory protein-1 are found after strenuous exercise. The concentration of IL-6 increases up to 100-fold after a marathon race. The increase in IL-6 is tightly related to the duration of the exercise and there appears to be a logarithmic relationship. Furthermore, the increase in IL-6 is related to the intensity of exercise. Given the facts that IL-6, more than any other cytokine, is produced in large amounts in response to exercise, that IL-6 is produced locally in the skeletal muscle in response to exercise and that IL-6 is known to have growth factor abilities, it is likely that IL-6 plays a beneficial role and may be involved in mediating exercise-related metabolic changes.     

Special feature for the Olympics: effects of exercise on the immune system: exercise effects on systemic immunity

Heavy exertion has acute and chronic influences on systemic immunity. In the resting state, the immune systems of athletes and non-athletes are more similar than disparate with the exception of NK cell activity, which tends to be elevated in athletes. Many components of the immune system exhibit adverse change after prolonged, heavy exertion. These immune changes occur in several compartments of the immune system and body (e.g. the skin, upper respiratory tract mucosal tissue, lung, blood and muscle). Although still open to interpretation, most exercise immunologists believe that during this 'open window' of impaired immunity (which may last between 3 and 72 h, depending on the immune measure) viruses and bacteria may gain a foothold, increasing the risk of subclinical and clinical infection. The infection risk may be amplified when other factors related to immune function are present, including exposure to novel pathogens during travel, lack of sleep, severe mental stress, malnutrition or weight loss.     

Special feature for the Olympics: effects of exercise on the immune system: exercise effects on mucosal immunity

The present review examines the effects of exercise on mucosal immunity in recreational and elite athletes and the role of mucosal immunity in respiratory illness. Habitual exercise at an intense level can cause suppression of mucosal immune parameters, while moderate exercise may have positive effects. Saliva is the most commonly used secretion for measurement of secretory antibodies in the assessment of mucosal immune status. Salivary IgA and IgM concentrations decline immediately after a bout of intense exercise, but usually recover within 24 h. Training at an intense level over many years can result in a chronic suppression of salivary immunoglobulin levels. The degree of immune suppression and the recovery rates after exercise are associated with the intensity of exercise and the duration or volume of the training. Low levels of salivary IgM and IgA, particularly the IgA1 subclass, are associated with an increased risk of respiratory illness in athletes. Monitoring mucosal immune parameters during critical periods of training provides an assessment of the upper respiratory tract illness risk status of an individual athlete. The mechanisms underlying the mucosal immune suppression are unknown.     

Special feature for the Olympics: effects of exercise on the immune system: exercise-induced modulation of macrophage function

Macrophages are important effector cells involved in phagocytosis, microbial killing and antitumour activity. Macrophages also display accessory cell function, in that they can present antigen to foster the development of T lymphocyte-mediated immunity. Recent work, including studies from this group, has demonstrated that acute and chronic exercise can affect many facets of macrophage biology. Manifestation of these effects depends on exercise intensity and duration, the function measured, the timing of measurement in relation to exercise and the concentration of the macrophage-activating stimulus. Exercise has potent stimulatory effects on phagocytosis, antitumour activity, reactive oxygen and nitrogen metabolism, and chemotaxis. Indeed, it has been shown that exercise training can increase macrophage antitumour activity in mice of different ages. However, not all functions are enhanced by exercise. Exercise-induced reductions in macrophage MHC II expression and antigen-presentation capacity have been documented. These findings bring up the possibility that exercise, and perhaps other stressors, activate macrophages for effector functions while downregulating accessory cell functions. To a large extent, the mechanisms responsible for the exercise-induced changes in macrophage function remain unknown, but may depend on exercise-induced changes in neuroendocrine factors. Future studies need to explore the effects in a mechanistic way and provide documentation as to their physiological significance.     

Special feature for the Olympics: effects of exercise on the immune system. Overview: exercise immunology

The review articles in this special feature reflect the current status of knowledge in the field of exercise immunology, with a focus on how exercise affects the human immune system and the health implications for resistance to infections and neoplastic diseases. In an Olympic year, the emphasis of exercise immunology research tends to be on elite athletes and the prevention of infections in the quest for optimum performance. However, research presented in this issue also covers recreational athletes, as well as highlighting the benefits of exercise for our ageing population.     

Special feature for the Olympics: effects of exercise on the immune system: effects of exercise on the immune system in the elderly population

Immunosenescence is characterized by impaired cellular immune function concomitant with increased inflammatory activity. Immune dysfunction is associated with increased mortality risk in elderly people. An important part of human ageing is characterized by a decline in the ability of individuals to adapt to environmental stress. Exercise has been suggested as a prototype for studying the effects of stress factors on the cellular immune system. Studies of interactions between an acute bout of exercise and immune function may be a useful and an ethically acceptable tool to investigate cell trafficking, immune mobilization/deficiency and the acute phase response during physical stress situations in relation to human ageing. Elderly humans have a preserved ability to recruit T lymphocytes and NK cells in response to an acute bout of exercise. Physical exercise training programs do not result in major restoration of the senescent immune system in humans. However, highly conditioned elderly humans seem to have a relatively better preserved immune system, although it is not possible to conclude if this is linked to training or other lifestyle-related factors.     

Special feature for the Olympics: effects of exercise on the immune system: infections and exercise in high-performance athletes

The elite athlete has a potentially increased sensitivity to respiratory infections, rendering protective measures particularly important. Some other infections that may appear in clusters in the sports setting, such as gastroenteritis, leptospirosis, herpes simplex and viral hepatitis, also require special precautionary attention. Strenuous exercise during ongoing infection and fever may be hazardous and should always be avoided. In addition, early symptoms of infection warrant caution until the nature and severity of the infection become apparent. Because myocarditis may or may not be accompanied by fever, malaise or catarrhal symptoms, athletes should be informed about the symptoms suggestive of this disease. Although sudden unexpected death resulting from myocarditis is rare, exercise should be avoided whenever myocarditis is suspected. Guidelines are suggested for the management and counselling of athletes suffering from infections, including recommendations on when to resume training. Acute febrile infections are associated with decreased performance resulting from muscle wasting, circulatory deregulation and impaired motor coordination, which require variable amounts of time to become normalized once the infection is over.     

Special feature for the Olympics: effects of exercise on the immune system: overview of the epidemiology of exercise immunology

The application of epidemiological methods to exercise immunology is reviewed briefly, with particular reference to the possible influences of physical activity, exercise and training on susceptibility to upper respiratory infections. Available reports are arbitrarily rated in terms of limiting factors: the quality of the assessment of physical activity, the precision of diagnosis of upper respiratory infection and overall methodology. The pattern of physical activity has often been clearly established but, in part because of the problems associated with the competitive environment, assessments of infection and overall methodology have often been less than optimal. Although there is some evidence that susceptibility to infection is increased by either a single bout of very heavy activity or a period of heavy training, reports are far from unanimous, and in certain respects fail to meet the classical epidemiological criteria of a causal relationship. The issue is important to both the health and the success of the international competitor, and merits definitive investigation, using optimal methods to assess both activity patterns and infection.     

Special feature for the Olympics: effects of exercise on the immune system: overtraining effects on immunity and performance in athletes

Overtraining is a process of excessive exercise training in high-performance athletes that may lead to overtraining syndrome. Overtraining syndrome is a neuroendocrine disorder characterized by poor performance in competition, inability to maintain training loads, persistent fatigue, reduced catecholamine excretion, frequent illness, disturbed sleep and alterations in mood state. Although high-performance athletes are generally not clinically immune deficient, there is evidence that several immune parameters are suppressed during prolonged periods of intense exercise training. These include decreases in neutrophil function, serum and salivary immunoglobulin concentrations and natural killer cell number and possibly cytotoxic activity in peripheral blood. Moreover, the incidence of symptoms of upper respiratory tract infection increases during periods of endurance training. However, all of these changes appear to result from prolonged periods of intense exercise training, rather than from the effects of overtraining syndrome itself. At present, there is no single objective marker to identify overtraining syndrome. It is best identified by a combination of markers, such as decreases in urinary norepinephrine output, maximal heart rate and blood lactate levels, impaired sport performance and work output at 110% of individual anaerobic threshold, and daily self-analysis by the athlete (e.g. high fatigue and stress ratings). The mechanisms underlying overtraining syndrome have not been clearly identified, but are likely to involve autonomic dysfunction and possibly increased cytokine production resulting from the physical stress of intense daily training with inadequate recovery.     

Special feature for the Olympics: effects of exercise on the immune system: modification of immune responses to exercise by carbohydrate, glutamine and anti-oxidant supplements

Immunosuppression in athletes involved in heavy training is undoubtedly multifactorial in origin. Training and competitive surroundings may increase the athlete's exposure to pathogens and provide optimal conditions for pathogen transmission. Heavy prolonged exertion is associated with numerous hormonal and biochemical changes, many of which potentially have detrimental effects on immune function. Furthermore, improper nutrition can compound the negative influence of heavy exertion on immunocompetence. An athlete exercising in a carbohydrate-depleted state experiences larger increases in circulating stress hormones and a greater perturbation of several immune function indices. The poor nutritional status of some athletes may predispose them to immunosuppression. For example, dietary deficiencies of protein and specific micronutrients have long been associated with immune dysfunction. Although it is impossible to counter the effects of all of the factors that contribute to exercise-induced immunosuppression, it has been shown to be possible to minimize the effects of many factors. Athletes can help themselves by eating a well-balanced diet that includes adequate protein and carbohydrate, sufficient to meet their energy requirements. This will ensure a more than adequate intake of trace elements without the need for special supplements. Consuming carbohydrate (but not glutamine or other amino acids) during exercise attenuates rises in stress hormones, such as cortisol, and appears to limit the degree of exercise-induced immunosuppression, at least for non-fatiguing bouts of exercise. Evidence that high doses of anti-oxidant vitamins can prevent exercise-induced immunosuppression is also lacking.     

Vaccination againstBoophilus microplus: Localization of antigens on tick gut cells and their interaction with the host immune system

Cattle have been vaccinated againstBoophilus microplus with antigens derived from partially fed female ticks. The immune response of the host lyses the gut cells of adult ticks, causing a reduction in the number, weight and reproductive capacity of engorging ticks. This response is different from the immunity that cattle acquire after repeated tick infestation. Evidence is presented that the antigens used in vaccination are located on the plasma membrane of the gut cells and it is unlikely that these antigens are secreted into the host during feeding. Vaccination using such concealed antigens may not encounter the mechanisms of immune evasion that parasites usually demonstrate.In-vitro assays suggest that vaccination immunity is not dependent on the need to stimulate cell-mediated responses. Immunoglobulin G alone, or with the aid of complement, is enough to damage tick gut.The normal function of the one protein antigen isolated so far is unknown but we speculate that it serves some vital function on the cell plasma membrane.     

Estradiol treatment and its interaction with the cholinergic system: effects on cognitive function in healthy young women

The steroid hormone estradiol has been shown to modulate cognitive function in both animals and humans, and although the exact mechanisms associated with these effects are unknown, interactions with the cholinergic system have been proposed. We examined the neurocognitive effects of short-term estradiol treatment and its interaction with the cholinergic system using the muscarinic receptor antagonist scopolamine in healthy young women. Thirty-four participants (Mean age ± SD = 22.4 ± 4.4) completed baseline cognitive assessment and then received either 100 μg/day transdermal estradiol or transdermal placebo for 31 days. On days 28 and 31 of treatment, further cognitive assessment was performed pre- and 90 min post-scopolamine (0.4 mg) or placebo (saline) injection, under a randomized double-blind placebo-controlled design. Short-term estradiol treatment significantly enhanced spatial working memory with a trend for improvement in long-term verbal learning and memory. Overall, estradiol treatment did not protect against or attenuate the scopolamine-induced impairments in the cognitive domains assessed. Findings suggest that estrogen has minimal effects on cholinergic-mediated cognitive processes following short-term treatment. Effects of estradiol treatment may be dependent on age, dose of estradiol, integrity of cholinergic innervation and baseline endogenous estrogen levels, which may in part explain the inconsistent findings in the literature.     

Review of factors essential for blastocyst implantation for their modulating effects on the maternal immune system

Pituitary and ovarian hormones prepare the endometrium for successful blastocyst implantation and support its process directly or indirectly through the action of growth factors, cytokines and other molecules. Many of the blastocyst implantation essential factors (BIEFs) are modulators of the maternal immune system. Since little is known as to the action of these molecules on the uterine lymphocytes, its clarification is imperative to the understanding of the process of blastocyst implantation.     

Biomarkers of effects: the immune system

© 2005 Wiley Periodicals, Inc. J Biochem Mol Toxicol 19:177–179, 2005; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/jbt.20075     

Rodent trypanosomes: their conflict with the immune system of the host

Rodent trypanosome infections provide the opportunity to study major phenomena that are displayed in many parasite-host combinations and, therefore, the chance to contribute to the elucidation of those phenomena. Here, Julia and Joseph Albright focus on the immune responses to rodent trypanosomes and on the tricks the parasites play to minimize the effects of those responses.     

Effects of eccentric exercise on the immune system in men

The effects of eccentric exercise on changes innumbers of circulating leukocytes, cell activation, cell adhesion, andcellular memory function were investigated in 12 men, aged 22-35yr. The immunologic effects of postexercise epidermal treatment withmonochromatic, infrared light were also evaluated. Blood was drawnbefore and 6, 24, and 48 h after exercise for phenotyping and analysisof creatine kinase activity. There was an increase in leukocyte, monocyte, and neutrophil number, no change in the number of basophils, eosinophils, B cells, and T cells, and a decrease in natural killer cell number postexercise. Some markers of lymphocyte and monocyte activation remained unchanged or decreased, whereas the expression ofadhesion molecules 62L and 11b increased on monocytes. It is concludedthat eccentric exercise induced decreased activation, and increasedcell adhesion capacity, of monocytes. Altered trafficking of cellsbetween lymphoid tissue and blood, selective apoptosis, orattachment/detachment from the endothelial wall can explain theobserved phenotypic changes. Treatment with monochromatic, infraredlight did not significantly affect any of the investigated variables.Correlations between immunologic and physiological parameters indicatea role of the immune system in adaptation to physical exercise.