An ever-growing volume of peer-reviewed publications speaks to the recent and rapid growth in both scope and understanding of exercise immunology. Indeed, more than 95% of all peer-reviewed publications in exercise immunology (currently >2, 200 publications using search terms "exercise" and "immune") have been published since the formation of the International Society of Exercise and Immunology (ISEI) in 1989 (ISI Web of Knowledge). We recognise the epidemiological distinction between the generic term "physical activity" and the specific category of "exercise", which implies activity for a specific purpose such as improvement of physical condition or competition. Extreme physical activity of any type may have implications for the immune system. However, because of its emotive component, exercise is likely to have a larger effect, and to date the great majority of our knowledge on this subject comes from exercise studies.

Position statement. Part one: Immune function and exercise.

Summary 1. A growing number of ecologists are turning to the enumeration of white blood cells from blood smears (leukocyte profiles) to assess stress in animals. There has been some inconsistency and controversy in the ecological literature, however, regarding their interpretation. The inconsistencies may stem partly from a lack of information regarding how stress affects leukocytes in different taxa, and partly from a failure on the part of researchers in one discipline to consult potentially informative literature from another. 2. Here, we seek to address both issues by reviewing the literature on the leukocyte response to stress, spanning the taxa of mammals (including humans), birds, amphibians, reptiles and fish. 3. We show that much of the early literature points to a close link between leukocyte profiles and glucocorticoid levels. Specifically, these hormones act to increase the number and percentage of neutrophils (heterophils in birds and reptiles), while decreasing the number and percentage of lymphocytes. This phenomenon is seen in all five vertebrate taxa in response to either natural stressors or exogenous administration of stress hormones. For the ecologist, therefore, high ratios of heterophils or neutrophils to lymphocytes (‘H : L’ or ‘N : L’ ratios) in blood samples reliably indicate high glucocorticoid levels. Furthermore, this close relationship between stress hormones and N : L or H : L ratios needs to be highlighted more prominently in haematological assessments of stress, as it aids the interpretation of results. 4. As with hormone assays, there are challenges to overcome in the use of leukocytes profiles to assess levels of stress; however, there are also advantages to this approach, and we outline each. Given the universal and consistent nature of the haematological response to stress, plus the overwhelming evidence from the veterinary, biomedical and ecological literature reviewed here, we conclude that this method can provide a reliable assessment of stress in all vertebrate taxa.

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The use of leukocyte profiles to measure stress in vertebrates: a review for ecologists

Over the last 20 years, heart rate monitors (HRMs) have become a widely used training aid for a variety of sports. The development of new HRMs has also evolved rapidly during the last two decades. In addition to heart rate (HR) responses to exercise, research has recently focused more on heart rate variability (HRV). Increased HRV has been associated with lower mortality rate and is affected by both age and sex. During graded exercise, the majority of studies show that HRV decreases progressively up to moderate intensities, after which it stabilises. There is abundant evidence from cross-sectional studies that trained individuals have higher HRV than untrained individuals. The results from longitudinal studies are equivocal, with some showing increased HRV after training but an equal number of studies showing no differences. The duration of the training programmes might be one of the factors responsible for the versatility of the results. HRMs are mainly used to determine the exercise intensity of a training session or race. Compared with other indications of exercise intensity, HR is easy to monitor, is relatively cheap and can be used in most situations. In addition, HR and HRV could potentially play a role in the prevention and detection of overtraining. The effects of overreaching on submaximal HR are controversial, with some studies showing decreased rates and others no difference. Maximal HR appears to be decreased in almost all ‘overreaching’ studies. So far, only few studies have investigated HRV changes after a period of intensified training and no firm conclusions can be drawn from these results. The relationship between HR and oxygen uptake (VO2) has been used to predict maximal oxygen uptake (VO2max). This method relies upon several assumptions and it has been shown that the results can deviate up to 20% from the true value. The HR-VO2 relationship is also used to estimate energy expenditure during field conditions. There appears to be general consensus that this method provides a satisfactory estimate of energy expenditure on a group level, but is not very accurate for individual estimations. The relationship between HR and other parameters used to predict and monitor an individual’s training status can be influenced by numerous factors. There appears to be a small day-to-day variability in HR and a steady increase during exercise has been observed in most studies. Furthermore, factors such as dehydration and ambient temperature can have a profound effect on the HR-VO2 relationship.

Heart rate monitoring: applications and limitations.

This review examines the influence on heart rate variability (HRV) indices in athletes from training status, different types of exercise training, sex and ageing, presented from both cross-sectional and longitudinal studies. The predictability of HRV in over-training, athletic condition and athletic performance is also included. Finally, some recommendations concerning the application of HRV methods in athletes are made.The cardiovascular system is mostly controlled by autonomic regulation through the activity of sympathetic and parasympathetic pathways of the autonomic nervous system. Analysis of HRV permits insight in this control mechanism. It can easily be determined from ECG recordings, resulting in time series (RR-intervals) that are usually analysed in time and frequency domains. As a first approach, it can be assumed that power in different frequency bands corresponds to activity of sympathetic (0.04-0.15 Hz) and parasympathetic (0.15-0.4 Hz) nerves. However, other mechanisms (and feedback loops) are also at work, especially in the low frequency band. During dynamic exercise, it is generally assumed that heart rate increases due to both a parasympathetic withdrawal and an augmented sympathetic activity. However, because some authors disagree with the former statement and the fact that during exercise there is also a technical problem related to the non-stationary signals, a critical look at interpretation of results is needed. It is strongly suggested that, when presenting reports on HRV studies related to exercise physiology in general or concerned with athletes, a detailed description should be provided on analysis methods, as well as concerning population, and training schedule, intensity and duration. Most studies concern relatively small numbers of study participants, diminishing the power of statistics. Therefore, multicentre studies would be preferable. In order to further develop this fascinating research field, we advocate prospective, randomised, controlled, long-term studies using validated measurement methods. Finally, there is a strong need for basic research on the nature of the control and regulating mechanism exerted by the autonomic nervous system on cardiovascular function in athletes, preferably with a multidisciplinary approach between cardiologists, exercise physiologists, pulmonary physiologists, coaches and biomedical engineers.

Heart rate variability in athletes.

Monitoring an athlete's physiological status in response to various types and volumes of (aerobic-oriented) training can provide useful information for optimizing training programs. Measures of resting, exercise and recovery heart rate (HR) are receiving increasing interest for monitoring fatigue, fitness and endurance performance responses, which has direct implications for adjusting training load 1) daily during specific training blocks and 2) throughout the competitive season. These measures are still not widely implemented to monitor athletes’ responses to training load, probably because of apparent contradictory findings in the literature. In this review I contend that most of the contradictory findings are related to methodological inconsistencies and/or misinterpretation of the data rather than to limitations of heart rate measures to accurately inform on training status. I also provide evidence that measures derived from 5-min (almost daily) recordings of resting (indices capturing beat-to-beat changes in HR, reflecting parasympathetic activity) and submaximal exercise (30- to 60-s average) HR are likely the most useful monitoring tools. For appropriate interpretation at the individual level, changes in a given measure should be interpreted by taking into account the error of measurement and the smallest important change of the measure, as well as the training context (training phase, load and intensity distribution). The decision to use a given measure should be based upon the level of information that is required by the athlete, the marker’s sensitivity to changes in training status and the practical constrains required for the measurements. However, measures of HR cannot inform on all aspects of wellness, fatigue and performance, so their use in combination with daily training logs, psychometric questionnaires and non-invasive, cost-effective performance tests such as a countermovement jump may offer a complete solution to monitor training status

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Monitoring training status with HR measures: do all roads lead to Rome?

This review focuses on the response of "stress" hormones to heat, exercise (single or repeated bouts), and combinations of these stimuli, with particular reference to their impact upon immune function. Very hot conditions induce a typical stress response, with secretion of catecholamines and cortisol. The catecholamines induce a demargination of leukocytes, and cortisol subsequently causes cells to migrate to lymphoid tissue. Sustained exercise, even in a thermally comfortable environment, induces a larger hormonal response than moderate thermal stress. With moderate exercise, increases in leukocyte numbers are related mainly to plasma norepinephrine concentrations, but with more intense exercise epinephrine concentrations assume a major importance. As exercise continues, plasma cortisol levels also rise, inducing an influx of neutrophils from bone marrow and an efflux of other leukocyte subsets. A combination of exercise and heat stress augments both hormonal and leukocyte responses. But these changes seem to be reversed if temperatures are clamped by exercising in cold water. If a second bout of exercise is performed with an inter-test interval of 30-45 min, neither hormone concentrations nor immune responses show any great cumulative effect under temperate conditions. However, in a hot environment the second exercise bout induces a larger and more persistent neutrophilia. Training influences these various responses mainly by decreasing the stress imposed when exercising at a given absolute work-rate.

Stress Hormones and the Immunological Responses to Heat and Exercise

Coaches and athletic team physicians have provided anecdotal information and case studies to support their beliefs that athletes may be unusually prone to illness during strenuous training or competition. Many athletes, in contrast, believe that physical activity improves their resistance to infectious disease. However, it is generally agreed that the stress of competition may make athletes temporarily more susceptible to infectious illness. A review of the literature shows that upper respiratory tract infections and skin infections are more prevalent in top level athletes than in the general population, particularly during periods of intensive training. Exercise induced changes occur in both the innate and adaptive components of the immune system; however, the relative importance of each component is unknown. Strenuous exertion and contact sports may compromise host defence both by reducing physical protection and by impairing immunosurveillance. Skin lacerations, vigorous sweating and maceration of the dermis impair the defence normally provided by the skin surface. In addition, adverse changes in soluble and cellular components of the immune system can increase susceptibility to infection. Persistence with strenuous training during an infectious illness can have deleterious effects; not only is athletic performance impaired, but the severity of the disease process can be augmented.

https://link.springer.com/content/pdf/10.2165%2F00007256-199417020-00002.pdf

Infection in Athletes

To determine if heat exposure alters the hormonal responses to moderate, repeated exercise, 11 healthy male subjects [age = 27.1 (3.0) years; maximal oxygen consumption, V˙O2max = 47.6 (6.2) ml · kg · min−1; mean (SD)] were assigned to four different experimental conditions according to a randomized-block design. While in a thermoneutral (23°C) or heated (40°C, 30% relative humidity) climatic chamber, subjects performed either cycle ergometer exercise (two 30-min bouts at ≈50% V˙O2max, separated by a 45-min recovery interval, CEx and HEx conditions), or remained seated for 3 h (CS and HS conditions). Blood samples were analyzed for various exercise stress hormones [epinephrine (E), norepinephrine (NE), dopamine, cortisol and human growth hormone (hGH)]. Passive heating did not alter the concentrations of any of these hormones significantly. During both environmental conditions, exercise induced significant (P < 0.001) elevations in plasma E, NE and hGH levels. At 23°C during bout 1: E = 393 (199) pmol · l−1 (CEx) vs 174 (85) pmol · l−1 (CS), NE = 4593 (2640) pmol · l−1 (CEx) vs 1548 (505) pmol · l−1 (CS), and hGH = 274 (340) pmol · l−1 (CEx)vs 64 (112) pmol · l−1 (CS). At 40°C, bout 1: E = 596 (346) pmol · l−1 (HEx) vs 323 (181) pmol · l−1 (HS), NE = 7789 (5129) pmol · l−1 (HEx) vs 1527 (605) pmol · l−1 (HS), and hGH = 453 (494) pmol · l−1 (HEx) vs 172 (355) pmol · l−1 (HS). However, concentrations of plasma cortisol were increased only in response to exercise in the heat [HEx = 364 (168) nmol · l−1 vs HS = 295 (114) nmol · l−1). Compared to exercise at room temperature, plasma levels of E, NE and cortisol were all higher during exercise in the heat (P < 0.001 in all cases). The repetition of exercise did not significantly alter the pattern of change in cortisol or hGH levels in either environmental condition. However, repetition of exercise in the heat increased circulatory and psychological stress, with significantly (P < 0.001) higher plasma concentrations of E and NE. These results indicate a differential response of the various stress hormones to heat exposure and repeated moderate exercise.

The impact of heat exposure and repeated exercise on circulating stress hormones

This study examined indices of parasympathetic (PNS) and sympathetic (SNS) nerve activity during exposure to heat and/or two successive bouts of exercise. Seven healthy males [age = 27.1 (3.6) years; mean (SD), maximum oxygen consumption (V˙O2

 max
 )= 48.1 (7.6) ml · kg−1 · min−1] were assigned to each of four experimental conditions according to a randomized-block design. While in a thermoneutral (23°C) or heated (40°C, 30% relative humidity) climatic chamber subjects performed exercise on a cycle ergometer (two 30-min bouts at ≈50% V˙O2

 max
 , separated by a 45-min recovery period, (CEx and HEx, respectively) or remained seated (CS and HS, respectively) for 2 h. The R-R intervals of the subjects' ECGs were analyzed for selected near-steady-state time periods [termed Phase I (25–40 min) and Phase II (100–115 min)] according to the method of Yamamoto and Hughson (J Appl Physiol 71:1143–1150, 1991). Total (PT), low-frequency (PLF = 0–0.15 Hz) and high-frequency (PHF = 0.15–0.5 Hz) power spectra were calculated using coarse-graining spectral analysis. Heat exposure alone did not alter autonomic balance or levels of circulating catecholamines significantly. Exercise in both environmental conditions induced a significant decrease in an index of PNS tone (PHF : PT) [PNS indicator for CS = 0.084 (0.04) vs CEx = 0.023 (0.015) and HS = 0.065 (0.027) vs HEx = 0.015 (0.009)], with an increase in catecholamine concentrations. Although the index of SNS activity (PLF:PHF) tended to rise with exercise in both environmental conditions, increments reached levels of significance only during exercise in the heat [SNS indicator for CS = 8.22 (5.58) vs CEx = 34.06 (21.73) and HS = 8.94 (5.49) vs HEx = 54.29 (49.80)]. The relative magnitudes of SNS and PNS indicators did not differ significantly between the first and second bouts of exercise. These results indicate the substantial contribution of vagal withdrawal and catecholamine secretion to the increase in heart rate that occurs during repeated moderate exercise at room temperature and the additional contribution from SNS activity during such exercise in the heat.

Spectral analysis of heart rate variability during heat exposure and repeated exercise.

Minimal information is available on the autonomic response to exercise under adverse environmental conditions. Traditionally, pharmacological blockade has been used to study autonomic responsiveness but, owing to its invasive nature, such studies have been limited in their scope. Recent advances in electrocardiographic tape recording, telemetry and associated computing systems have provided investigators with noninvasive methods for assessing the autonomic response to various physiological stressors. This article describes methods for the analysis of heart rate variability (HRV) and discusses the reports of those who have used HRV analysis to evaluate autonomic regulation during exercise, heat exposure and the combination of these 2 stressors.

Ingrid K. M. Brenner

Papers

Stress Hormones and the Immunological Responses to Heat and Exercise

Infection in Athletes

The impact of heat exposure and repeated exercise on circulating stress hormones

Spectral analysis of heart rate variability during heat exposure and repeated exercise.

Autonomic Regulation of the Circulation During Exercise and Heat Exposure Inferences from Heart Rate Variability