Exercise, immune function and respiratory infection:

 Exercise, immune function and respiratory infection: An update on the influence of training and environmental stress .

Abstract

This review outlines recent advancements in the understanding of athlete immune health. Controversies discussed include whether high levels of athletic training and environmental stress (for example, heat acclimation, cryotherapy and hypoxic training) compromise immunity and increase upper respiratory tract infection (URTI). Recent findings challenge early exercise immunology doctrine by showing that international athletes performing high-volume training suffer fewer, not greater, URTI episodes than lower-level performers and URTI incidence decreases, not increases, around the time of competition compared with heavy training. Herein we raise the possibility of host genetic influences on URTI and modifiable behavioural and training-related factors underpinning these recent observations. Continued controversy concerns the proportion of URTI symptoms reported by athletes that are due to infectious pathogens, airway inflammation or as yet unknown causes and indeed whether the proportion differs in athletes and non-athletes. Irrespective of the cause of URTI symptoms (infectious or non-infectious), experts broadly agree that self-reported URTI hinders high-volume athletic training but, somewhat surprisingly, less is known about the influence on athletic performance. In athletes under heavy training, both innate and acquired immunity are often observed to decrease, typically 15–25%, but whether relatively modest changes in immunity increase URTI susceptibility remains a major gap in knowledge. With the exception of cell-mediated immunity that tends to be decreased, exercising in environmental extremes does not provide an additional threat to immunity and host defence. Recent evidence suggests that immune health may actually be enhanced by regular intermittent exposures to environmental stress (for example, intermittent hypoxia training).

There has been a long since held belief that an acute bout of heavy exercise (>1.5-h duration) and chronic intensive exercise training (>1.5 h on most days) undertaken by endurance athletes compromises host defence and increases the incidence of upper respiratory tract infections (URTIs).1, 2 Seminal work published in 1982 by Tomasi et al.3 showed lower levels of saliva immunoglobulin-A (IgA) in cross-country skiers at rest compared with age-matched controls and a further reduction in saliva IgA after competition. This decrease in immune defence was thought to provide an ‘open window’ for opportunistic infections (for example, URTIs such as the common cold).4, 5 To date, there are >3500 peer-reviewed publications using the search terms ‘exercise’ and ‘immune’ (ISI Web of Science), approximately 1100 of which have been published since the Exercise Immunology Review position statements in 2011.6, 7 Accordingly, an update is warranted and timely ahead of the 2016 Olympic Games and our aim herein is to review recent advancements, discuss continued controversies and outline some important research questions for exercise immunologists moving forward. First, we review the effects of heavy exercise and intensive exercise training on URTI and immunity, with particular focus on whether elite athletes do indeed suffer increased URTI and whether the changes in immunity observed are meaningful. Then we review the effects of exercising in environmental extremes on URTI and immunity. This is pertinent because although the average ambient conditions in Rio at the time of the 2016 summer Olympics might not be considered severe (24 °C, RH 66%) temperatures may well exceed 28 °C; indeed, exercising in the heat has been proposed to provide an additional threat to immunity.8 In addition, as part of their preparation and training, athletes will likely utilise hypoxia, cryotherapy and heat exposure, all of which can influence immunity and will be the focus of the second part of this review.

Exercise and upper respiratory infection: what do we know and what do we still have to learn?

Central to the doctrine of early exercise immunology was that athletes who engage in high-volume endurance training succumb to a greater incidence of URTIs than their less-active counterparts. Though there is some evidence to support this notion,1, 2, 9 recent work indicates that an important distinction be made between athletes at national and international level.10, 11 As logic dictates, a high training volume as would be required by an international endurance athlete is incompatible with frequent URTI.10 Empirical evidence, albeit in a small number of athletes, indicates that international athletes suffer fewer URTI episodes than national-level athletes11 and that URTI correlates negatively with training load, namely, ‘the less sick the more the athlete can train’.10 Another recent study performed prospectively in a large cohort of 1509 Swedish men and women also showed that high levels of physical activity (~1 h exercise per day) reduced the incidence of URTI.12 At first glance, these recent studies appear to challenge the J-shaped curve depicting the relationship between the dose of exercise and URTI risk.13 However, there may be genetic and/or modifiable behavioural factors that account for why international athletes succumb to fewer URTIs than national-level athletes during high-volume training. For example, there may be host genetic influences on URTI14 whereby elite athletes are predisposed to have a more efficacious immune response to challenge with respiratory viruses, but this Darwinian hypothesis remains to be investigated in athletes. To date, the evidence for a genetic predisposition to respiratory infections such as seasonal influenza is mostly circumstantial (for example, host risk factors during the 2009 influenza pandemic included obesity and pregnancy),15 and little is known about genetic influences on susceptibility to the common cold. However, recent work in both mice and humans highlights important genetic influences (for example, IFITM3 and Mx1) in host susceptibility to influenza.15, 16 High-throughput screening platforms may, in the near future, present the opportunity to explore candidate genes for URTI risk in athletes. If future research supports this hypothesis, there are important considerations for how this information is used in the management of and care of athletes. For example, genetic screening might identify that a national-level athlete with future medal-winning prospects is at high risk of URTI, but with appropriate education about lifestyle behaviours (for example, infection avoidance), they may be able to cope with the high training volume required to reach international level with minimal disruption owing to URTI. It is quite conceivable that the observation of lower URTI incidence in international vs national athletes11 can be explained by improved lifestyle behaviours in international athletes that alter infection risk (for example, hygiene, infection avoidance, diet, sleep and stress management)7 as a result of experience and/or access to better education. It is also conceivable that international athletes who receive funding are less likely to have to balance a full-time job alongside their training and competition schedule and so experience less overall stress, which in turn could account for their reduced susceptibility to URTI. Notwithstanding the relatively unexplored possibility of a genetic predisposition to URTI, recent work11 puts in the spotlight some simple precautions and training strategies to avoid URTI in athletes (Table 1).7 In 28 professional swimmers monitored weekly over 4 years, the likelihood of URTI was increased during the winter in those with recent URTI episodes and during periods of high training load (both pool-based and dryland).11 The authors showed a 50% lower likelihood of URTI during periods of competition compared with periods of intensive training, which challenges the doctrine of early exercise immunology that suggested URTIs were particularly prevalent around the time of competitions.2, 6, 13

One continued controversy concerns the proportion of URTI symptoms reported by athletes that are due to infectious pathogens, airway inflammation or as yet unknown causes and indeed whether the proportion differs in athletes and non-athletes.6, 9 Although there is a popularly held belief that athletes are particularly prone to URTI symptoms of non-infectious origin, for example, allergy and inflammation,9, 17, 18 further rigorously controlled work including sufficient sample sizes of athletes and non-athletes is required to substantiate this claim. Unfortunately, few studies in athletes have verified the presence of infection by performing reverse transcription-PCR analysis on nasopharyngeal and throat swabs, with most relying on symptom questionnaires or physician-verified URTI; indeed, the validity of physician-verified URTI has come under scrutiny.17 The few studies that have performed pathogen detection in athletes reporting URTI symptoms,9, 17 and compared with sedentary controls,9 indicate that only approximately one-third of reported URTIs are due to respiratory pathogens.9, 17 This rather low rate of respiratory pathogen detection in athletes with URTI symptoms (~30%)9, 17 appears at odds with evidence that human rhinovirus caused 80% of self-diagnosed common colds in adults during the seasonal autumn peak.19 This discrepancy is likely because the studies in athletes were conducted year-round17 or during the southern hemisphere summer9 when common cold incidence is low and allergy incidence is high. Nevertheless, these studies highlight that self-reported or physician-verified URTI should not ubiquitously be referred to as infectious.9, 17 Perhaps most telling is that the proportion of individuals with pathogen-identified URTI was not lower in athletes (29%) compared with that in sedentary controls (22%).9 As such, these findings do not support the notion that athletes are more susceptible to URTI symptoms of non-infectious origin (for example, inflammation and allergy) than non-athletes. One study in 208 recreationally runners taking part in the London marathon indicated a postrace association between self-reported URTI symptoms and allergy assessed by questionnaire and a greater incidence of allergy in runners vs controls.18 These interesting findings require substantiating in a study comparing athletes and non-athletes using the gold-standard skin prick testing alongside specific IgE testing as the allergy questionnaire adopted demonstrated poor sensitivity (58%).18 Clearly, resolving this controversy represents a fruitful avenue for future research, the findings of which may direct preventative strategies and treatment. Future research is also required to verify and elucidate the findings of a recent study in 236 athletes demonstrating that previous coinfection with cytomegalovirus and Epstein Barr virus (N=50) resulted in 50% fewer URTI episodes in the winter, a finding the authors suggest represents improved immune surveillance.20 Irrespective of the cause of URTI symptoms (infectious or non-infectious), experts broadly agree that self-reported URTI hinders high-volume athletic training,10 but, somewhat surprisingly, less is known about the influence on athletic performance.21 Appropriately designed studies are sorely needed to disentangle infectious and non-infectious URTI symptoms and their influence on athletic performance.

Exercise and immunity: what do we know and what do we still have to learn?

It has long been known that acute and chronic exercise alters mucosal immunity3 and the number and function of circulating cells of the innate immune system (for example, neutrophils, monocytes and natural killer cells) and the acquired immune system (T and B lymphocytes).6 For example, T- and B-cell functions appear to be sensitive to increases in training load in well-trained athletes, with decreases in circulating numbers of type 1 T cells, reduced T-cell proliferative responses and falls in stimulated B-cell Ig synthesis.6 For a comprehensive review of the literature investigating the influence of exercise on immunity, readers are directed to the position statement of the ISEI (International Society of Exercise and Immunology).6 In addition, the neuro-endocrine modulation of immunity (for example, by glucocorticoids) in response to stressors such as exercise has very recently been reviewed by Dhabhar.22 Here we will provide a commentary on what we believe to be important recent advances and continued controversies that will guide future research endeavours with specific relevance, where available, to studies on immunity in well-trained athletes: the anti-inflammatory health benefits of short-lasting moderate physical activity are dealt with elsewhere in this special feature. Although the distinction between innate and acquired branches of the immune system is somewhat crude, and we recognize that these are inextricably linked (for example, via the innate immune system's role in antigen presentation), here we will focus first on innate and then on acquired cellular components.

Exercise and innate immunity

One of the major gaps in knowledge, and a key challenge for continued research endeavours, remains whether the observed changes in either innate or acquired immunity with acute and chronic exercise (typically 15–25%) in athletes alters host defence and disease susceptibility.6 For prohibitive reasons, likely related to cost, ethics and access, few studies have monitored clinically relevant immune measures and made parallel assessments of URTI in high-level athletes (and controls) over a season; as such, commentators are left speculating about a causal relationship between immunity and infection in athletes. For example, Hellard et al.11 elegantly demonstrated an ~10% increased risk of URTI in elite swimmers with ~10% increases in training load but made no measures of immune function. A recent study showed that a 3-day period of functional overreaching in both runners and cyclists decreased granulocyte and monocyte phagocytosis and oxidative burst activity by 14 and 38 h of recovery but did not compare URTI incidence in the period that followed with a control group.23 Experts agree that the impact of acute exercise and training on dendritic cells (DCs) remains poorly understood and a topic ripe for investigation particularly given the crucial role DCs have in initiating adaptive immune responses by presenting antigens and costimulatory molecules to T and B cells.6 Acute exercise has been shown to increase the number of circulating myeloid and plasmacytoid DCs,24 and recent work has shown that acute maximal exercise increases the ex vivo generation of monocyte-derived DCs,25 but the functional consequences of these observations remains poorly understood.

Exercise and acquired immunity

Given the important role of naive T cells in host defence against novel pathogens and infection susceptibility, the preferential mobilisation of senescent T cells into the circulation after heavy exercise is now thought to facilitate apoptosis and make space for newly functional T cells, namely, exercise expands the naive T-cell repertoire.26 Recent work indicates that high-level endurance training may contribute to premature age-associated changes to the T-cell compartment, namely, reduced thymic output assessed as low signal-joint T-cell receptor excision circle levels in circulating T cells of athletes vs age matched controls.27 Another recent study showed that 1 week of intensified training in trained male cyclists impaired the egress of naive CD8+ T lymphocytes (CD27+CD45RA+) and cytotoxic T lymphocytes from the blood after exercise.28 The authors suggested that smaller neuro-endocrine responses to exercise (reduced plasma epinephrine and cortisol) after intensified training could account for their findings that they believe indicate reduced immune surveillance. Preliminary work indicates that sex may moderate the effects of exercise on T-cell redistribution,29 and indeed other measures of immunity (reviewed elsewhere),30 but future work is required to elucidate a role for sex hormones. A recent study indicates that high training load in endurance athletes is associated with greater resting levels of circulating regulatory T cells (CD4+CD25+CD127low/−) and greater whole-blood antigen-stimulated interleukin-10 production.31 In another study, the same authors also showed that individuals with a high weekly physical activity (⩾7 h per week) had raised whole-blood antigen-stimulated interleukin-10 production and suffered on average more than twice as many URTIs during the winter months than those who exercised 3–6 h per week.32 Paradoxically, these immunoregulatory responses may impair the immune response to a new pathogen (raising URTI incidence) and suppress antitumor immunity,22 but the long-term effects of the enhanced anti-inflammatory state could be regarded as beneficial in counteracting low-grade inflammation and the associated risk of cardiovascular disease, type 2 diabetes mellitus, obesity and cancer.32

Moving forward, where feasible, exercise immunologists are encouraged to use in vivo immune methods. By initiating an integrated and highly coordinated immune response in the normal tissue environment, in vivo immune methods provide more clinically relevant information that extends beyond in vitro assays.33 A weakness of many in vitro assays is the requirement to separate immune cells from their normal environment and incubate in artificial culture. Examples of in vivo immune methods include assessing the circulating antibody response to influenza vaccination34 and the local skin response to intradermal antigens (delayed type hypersensitivity) or topically applied antigens (contact hypersensitivity).6, 33 In line with the acute-stress-induced immune-enhancement hypothesis,22 studies demonstrate that exercise increases influenza vaccination success (circulating antibody titre) in those with sub-optimal immunity (for example, elderly) or where antigen immunogenicity is low; but little is known about the influence of high-level training on the success of influenza vaccination.34 Recognized limitations with this method include that the ex vivo T-cell response to influenza vaccination has been more strongly related to vaccine protection than the circulating antibody titre.34 Also, the incorporation of repeat antigens in the influenza vaccine elicits a mixture of primary, secondary and tertiary antibody responses.6 Using a novel antigen presents the opportunity to assess the influence of exercise stress on both the induction of a new immune response and the recall of previously developed immunity. Our recent work using the skin contact sensitizer, diphenylcyclopropenone (DPCP) demonstrates that 2 h of treadmill running at 60% V̇O2peak decreases both the induction (−67%: Figure 1a) of T-cell mediated immunity33 and recall response (−19%: Figure 1d)35 in subjects who, after repeated monthly exposures achieved a reproducible plateaux in skin responses to DPCP (Figure 1c). That we showed no effect of prolonged moderate-intensity exercise on the skin's response to the irritant croton oil (Figure 1b) points towards a suppression of cell-mediated immunity. These data also challenge the concept that short-lasting, high-intensity endurance exercise decreases immunity as 30 min running at 80% V̇O2peak did not influence immune induction to DPCP (Figure 1a). These findings support the recommendation that athletes should consider replacing some of their long-duration, moderate-intensity training bouts with shorter spike sessions to limit training-induced immune impairments (Table 1).7 This work might also help explain why URTI symptoms are reduced in high-level swimmers during the taper period when overall training volume is reduced but intensity remains high.11 Given that DPCP is benign, determining the clinical significance of the response with specific regard to infection (skin and other) is an important avenue for future research. Preferably, the strength of the cutaneous recall response to DPCP could be generalized beyond skin immunity to indicate the immune system's general ability to respond to an infectious challenge, but this requires investigation.

Environmental stress, URTI and immune function: what do we know and what do we still have to learn?

During regular training and competition, many athletes experience exertional hyperthermia (core temperature >39.5 °C), dehydration, peripheral cooling and moderate altitude or hypoxia (up to ~2500 m).36, 37 Athletes are also exposed to environmental stress outside of training. For example, during long-haul air travel, which is common for elite athletes, hypobaric-hypoxia in the aircraft cabin exposes athletes to altitudes equivalent to 1800–2400 m.38 A few athletes also experience more extreme thermal stress such as exertional heat illness casualties (core temperatures can be >41 °C) and hypothermic casualties (core temperature <35 °C, for example, open water swimmers), and high altitude (up to 5000 m) is experienced in athletes participating in adventure races or intermittent hypoxic training. Sports performance typically decreases in hot, cold and high-altitude environments, although there are notable exceptions such as improved sprint and jump performance at altitude36 and the improved endurance exercise performance in cool environments.39 Performance is impaired because exercising in extreme environments increases demands on the central nervous system, cardiovascular system and on metabolism. The body's response to the challenge of exercise, thermal stress or hypoxia is initiated and coordinated by the central nervous system and the effector limbs of the hypothalamic–pituitary–adrenal axis and sympatheticoadrenal–medullary axis that produce the immunoregulatory hormones, such as cortisol, adrenaline and noradrenaline.22 It is therefore easy to understand why in the late 1990s, one of the pioneers of this field, Dr Roy Shephard hypothesized that exercise in adverse environments, with stereotyped stress hormone responses over and above that seen during exercise in favourable conditions, may cause greater disruption to immune function and host defence.8 For detailed discussion of earlier studies investigating the effects of environmental stress on immunity, readers are directed to the ISEI position statement and earlier reviews.7, 8, 40 Here we will provide a commentary on what we believe to be important recent advances and continued controversies that will guide future research endeavours with specific relevance, where available, to studies in athletes exercising or training in commonly encountered environments (for example, −10 to 40 °C air temperatures and <2500-m altitude).

Thermal stress and immunity

One continued controversy concerns whether exercising in or resting in hot or cold environments is harmful to an athlete's immune health. Laboratory studies where core temperature remains within 2 °C of normal baseline indicate a rather limited effect of either hot or cold environments on immune function, with the possible exception of T-cell-mediated immunity that has been reported to decrease (Table 2).41, 42 As such, most of the available evidence does not support the contention that exercising in the heat or cold poses a greater threat to immune function compared with thermoneutral conditions.7 It is worth noting that individuals exercising in hot (vs cool) conditions tend to fatigue sooner or reduce their work rate so their exposure to exercise stress in the heat tends to be self-limiting. Modest dehydration as a result of heavy training or competition in the heat (typically of the order of 1–4% body mass loss) has been under the spotlight recently in exercise immunology and exercise physiology. The belief held by some exercise immunologists is that dehydration may impair immune health of athletes as dehydration increases physiological strain and immunomodulatory stress hormones.43 Although recent evidence indicates that modest dehydration may transiently decrease mucosal immunity,44 the overwhelming balance of evidence suggests that modest dehydration typically experienced by athletes has relatively limited impact on exercise immune responses (Table 2).45, 46, 47 For example, very recent research shows that modest dehydration (~4% body mass loss) caused by fluid restriction and prolonged moderate-intensity exercise did not affect circulating antigen-stimulated cytokine production, tear fluid IgA or saliva antimicrobial responses, including IgA, lysozyme and lactoferrin.45, 46, 47 These recent exercise immunology findings harmonize with those from current research in exercise physiology that challenge the widely held belief that modest dehydration decreases exercise performance in the heat.48 One area of continued research interest, and the subject of a very recent review,49 focusses on the putative involvement of immune dysregulation and inflammation in altered thermal tolerance, exertional heat illness and heat stroke.7 Recent research showed that the inflammatory response to muscle-damaging exercise (increase in circulating interleukin-6, a known pyrogen) correlated positively (r=0.67) with the subsequent rise in core temperature during exercise heat stress 30 min later.50 Although an augmented inflammatory response may increase heat strain and the risk of heat illness during acute exercise heat stress, recent research points to an important role for inflammation in acquired cellular thermal tolerance (for example, cytoprotective role for heat-shock protein 70) and the more chronic phenotypic adaptations associated with heat acclimation.51 Research that provides a better understanding of acquired cellular thermal tolerance and its proposed role in the thermoregulatory adaptations with heat acclimation is sorely needed. As is research investigating the popular belief that regular sauna exposure reduces URTI incidence.52

Although not entirely conclusive, evidence indicates that cold exposure often precedes, and is associated with increased incidence of, URTIs, including the ‘common cold’.53 Further research is required to investigate the commonly held beliefs by athletes that breathing cold, dry air and getting a ‘chill’ through cooling of the skin causes the ‘common cold’. Although these beliefs are controversial, some evidence shows that peripheral cooling of the nose and upper airways (and even the feet) can increase common cold symptoms, possibly by inhibiting immune cell trafficking and creating a suitable local environment for viral replication.54 Somewhat at odds are the findings of another group showing that frequent cold water immersion has mild immuno-stimulatory effects.55 Although the benefits of cryotherapy for training adaptations have recently been questioned,56 postexercise cryotherapy in the form of cold water immersion or cold air exposure have become popular additions to athletic training and competition regimens; as such, the influence of these practices on immunity and host defence requires investigation.

Altitude stress and immunity

Altitude training typically involves athletes being exposed passively or while exercising in hypoxia for 1–6 h per day for 5–14 days. Although there is continued debate over the benefits to sport performance,57, 58 there is relatively little discussion and research about how various altitude-training methods affect immunity and host defence in athletes. This is concerning as the current consensus is that altitude and hypoxic exposure decrease both in vivo and in vitro cell-mediated immune function and increase self-reported respiratory infection (Table 2)38, 59, 60, 61, 62, 63, 64, 65, 66: this remains the case even when considering only studies involving high-level athletes (Table 3).59, 60, 64 Nevertheless, caution is required when interpreting findings from studies of self-reported URTI at altitude as there is considerable overlap between symptoms of upper airway infection and acute mountain sickness.63 One emerging trend from the literature is that immunity and host defence are typically decreased in studies where athletes complete live-high train-high or live-high train-low altitude training methods59, 60, 61, 64 but not in studies involving intermittent hypoxic training.67, 68, 69 Recent studies using intermittent hypoxic training actually describe favourable outcomes for immune measures, including reduced circulating senescent T-lymphocyte subsets68 and increased mucosal immunity69; although a limitation is that some of these studies were conducted in untrained individuals. As many forms of hypoxic training are now being used,57 future research should seek to determine how each of these altitude-training methods affect athlete immune function and URTI incidence.

Future research directions for the field of exercise immunology

Future investigations should disentangle the psychosocial and physiological underpinning of decreased immunity and host defence in high-level athletes. Given the well-known influence of psychological stress on immune function,22 it is quite conceivable that psychosocial stress status in high-level athletes (related to life stress, contractual issues, team selection, injury, travel, sleep disruption, jetlag and so on) accounts, at least in part, for the aforementioned alterations in, or modulates the influence of exercise on, immunity and host defence. The interesting observation in one recent study that URTI incidence was decreased by regular exercise in males reporting high but not low stress supports this concept.12 This and the concept of ‘stress reactivity’70 whereby both exaggerated and diminished responses to stress are hypothesised to increase the risk of illness remain topics ripe for investigation. By forging collaborations with experts in the ever-expanding field of psycho-neuro-immunology, exercise immunologists can apply their talents to answer these important questions in the near future.

Finally, the exercise scientist has, at their disposal, a rich and varied toolkit to assess training adaptation but not maladaptation and immune suppression. As such, exercise immunologists should continue their quest to identify field-worthy, non-invasive markers of immunity that can be used for this purpose. We very recently demonstrated that tear secretory IgA has potential as a non-invasive biomarker of mucosal immunity and common cold risk by showing decreased levels of tear secretory IgA the week before individuals reported URTI symptoms during the common cold season (Figure 2).45 This research is important not just because tear fluid is easily accessible but also because up to 95% of all infections are estimated to be initiated at the mucosal surfaces.71 Further advances in nanotechnology and microfluidics might, in the near future, afford the possibility for on-the-spot tear fluid measurement devices and continuous bio-monitoring by contact lenses.

CONFLICT OF INTEREST

The authors declare no conflict of interest.

Prolonged moderate-intensity exercise impairs both the induction and elicitation phases of the cell-mediated in vivo immune response in humans. (a) Effect of exercise stress prior to induction of contact hypersensitivity with DPCP on skin thickening response to challenge 28 days later. Shown are rested control group (CON); 30 min at 60% V̇O2peak (30MI); 30 min at 80% V̇O2peak (30HI) and 120 min at 60% V̇O2peak (120MI). (b) Effect of seated rest (CON) or prolonged exercise stress (120MI) on skin redness response to irritant challenge with croton oil (Panels a and b are adapted from Diment et al.33). (c) Repeated monthly DPCP exposures for 4 months boosts the skin thickening response to achieve a plateau. (d) Effect of prolonged exercise stress (120MI) on elicitation response to DPCP in participants who reached a plateaux in skin response to DPCP after monthly exposures for 4 months (Panel c and d are adapted from Harper Smith et al.35). #P<0.05 vs CON. *P<0.05 vs previous month challenge. Data are mean±s.d.

运动、免疫功能和呼吸道感染：关于训练和环境压力影响的最新信息。

 抽象的

 本综述概述了对运动员免疫健康理解的最新进展。 讨论的争议包括高水平的运动训练和环境压力（例如，热适应、冷冻疗法和缺氧训练）是否会损害免疫力并增加上呼吸道感染 (URTI)。 最近的发现挑战了早期运动免疫学学说，表明进行高强度训练的国际运动员比低水平运动员遭受更少而不是更多的 URTI 发作，并且与大量训练相比，在比赛期间 URTI 发生率下降而不是增加。 在此，我们提出了宿主遗传影响 URTI 的可能性，以及支持这些最近观察的可修改行为和训练相关因素。 持续的争议涉及运动员报告的由传染性病原体、气道炎症或未知原因引起的 URTI 症状的比例，以及运动员和非运动员的比例是否不同。 不管 URTI 症状的原因是什么（感染性或非感染性），专家们普遍同意自我报告的 URTI 会阻碍大量运动训练，但令人惊讶的是，人们对运动表现的影响知之甚少。 在接受大量训练的运动员中，通常观察到先天性和获得性免疫均降低，通常为 15-25%，但相对适度的免疫变化是否会增加 URTI 易感性仍然是一个主要的知识空白。 除了细胞介导的免疫趋于降低外，在极端环境中锻炼不会对免疫和宿主防御造成额外威胁。 最近的证据表明，定期间歇性地暴露于环境压力（例如，间歇性缺氧训练）实际上可能会增强免疫健康。

 长期以来，人们一直认为耐力运动员进行的剧烈运动（> 1.5 小时持续时间）和慢性高强度运动训练（大多数日子> 1.5 小时）会损害宿主防御并增加上呼吸道的发病率 感染 (URTIs)。1, 2 Tomasi 等人于 1982 年发表的开创性工作 3 显示，与年龄匹配的对照组相比，休息时越野滑雪者的唾液免疫球蛋白 A (IgA) 水平较低，并且唾液 IgA 水平进一步降低 比赛后。 这种免疫防御的降低被认为为机会性感染（例如，普通感冒等 URTI）提供了一个“开放窗口”。4, 5 迄今为止，有超过 3500 篇同行评议的出版物使用搜索词“锻炼” 和“免疫”（ISI Web of Science），自 2011 年 6 月发表运动免疫学评论立场声明以来，其中大约 1100 篇已发表，7 因此，在 2016 年奥运会之前有必要及时进行更新，我们在此的目的是回顾 最近的进展，讨论持续存在的争议，并概述了运动免疫学家前进的一些重要研究问题。 首先，我们回顾了剧烈运动和高强度运动训练对 URTI 和免疫力的影响，特别关注精英运动员是否确实患有 URTI 增加以及观察到的免疫变化是否有意义。 然后我们回顾了在极端环境中锻炼对 URTI 和免疫力的影响。 这是相关的，因为尽管 2016 年夏季奥运会期间里约的平均环境条件可能不被认为是严酷的（24 °C，相对湿度 66%），但温度可能会超过 28 °C； 事实上，有人提议在高温下锻炼会对免疫力造成额外威胁。 8 此外，作为准备和训练的一部分，运动员可能会利用缺氧、冷冻疗法和热暴露，所有这些都会影响免疫力，并将成为 本综述第二部分的重点。

 运动和上呼吸道感染：我们知道什么，我们还需要学习什么？

 早期运动免疫学学说的核心是，进行大量耐力训练的运动员比不那么活跃的运动员更容易患上 URTI。 尽管有一些证据支持这一观点，1, 2, 9 最近的工作表明，国家级和国际级运动员之间存在重要区别。 10, 11 按照逻辑，国际运动员需要大量训练。 耐力运动员与频繁的 URTI 不相容。 10 经验证据，尽管在少数运动员中，表明国际运动员遭受 URTI 发作的次数少于国家级运动员 11 并且 URTI 与训练负荷呈负相关，即“病得越少越多” 10 最近在 1509 名瑞典男性和女性的大型队列中前瞻性进行的另一项研究也表明，高水平的体育活动（每天约 1 小时的锻炼）降低了 URTI 的发生率。12 乍一看，这些 最近的研究似乎挑战了描述运动剂量与 URTI 风险之间关系的 J 形曲线。 13 然而，可能存在遗传和/或可改变的行为因素 解释了为什么国际运动员在高容量训练中比国家级运动员屈服于更少的 URTI 的原因。 例如，可能存在宿主遗传对 URTI14 的影响，即精英运动员倾向于对呼吸道病毒的挑战产生更有效的免疫反应，但这一达尔文假说仍有待在运动员中进行研究。 迄今为止，季节性流感等呼吸道感染的遗传易感性证据大多是间接的（例如，2009 年流感大流行期间的宿主风险因素包括肥胖和怀孕），15 并且对遗传对常见疾病易感性的影响知之甚少。 寒冷的。 然而，最近在小鼠和人类中的研究强调了宿主对流感易感性的重要遗传影响（例如，IFITM3 和 Mx1）。 15, 16 高通量筛选平台可能在不久的将来提供探索候选基因的机会 运动员的 URTI 风险。 如果未来的研究支持这一假设，那么对于如何在运动员的管理和护理中使用这些信息，有重要的考虑因素。 例如，基因筛查可能会发现有未来获得奖牌前景的国家级运动员患有 URTI 的高风险，但通过适当的生活方式行为教育（例如，避免感染），他们可能能够应对高风险。 达到国际水平所需的培训量，而 URTI 造成的干扰最小。 可以想象，国际运动员与国内运动员相比，URTI 发病率较低 11 可以通过改善国际运动员的生活方式行为来解释，从而改变感染风险（例如，卫生、避免感染、饮食、睡眠和压力管理）7 结果 经验和/或获得更好的教育。 也可以想象，获得资助的国际运​​动员不太可能需要在全职工作与训练和比赛日程之间取得平衡，因此整体压力较小，这反过来可能是他们对 URTI 的易感性降低的原因。 尽管 URTI 遗传易感性的可能性相对尚未探索，但最近的工作 11 将一些简单的预防措施和训练策略放在了聚光灯下，以避免运动员发生 URTI（表 1）。7 在 4 年内每周监测的 28 名专业游泳运动员中，URTI 的可能性是 最近发生 URTI 的人在冬季和高训练负荷期间（游泳池和旱地）增加。11 作者表明，与高强度训练期间相比，比赛期间发生 URTI 的可能性降低了 50%，这具有挑战性。 早期运动免疫学学说表明 URTIs 在比赛期间特别普遍。 2, 6, 13

 一项持续存在的争议涉及运动员报告的由传染性病原体、气道炎症或未知原因引起的 URTI 症状的比例，以及运动员和非运动员的比例是否存在差异。 6, 9 尽管人们普遍认为 运动员特别容易出现非感染性 URTI 症状，例如过敏和炎症，9, 17, 18 需要进一步严格控制的工作，包括运动员和非运动员的足够样本量来证实这一说法。 不幸的是，很少有运动员研究通过对鼻咽和喉咙拭子进行逆转录 PCR 分析来验证感染的存在，大多数研究依赖于症状问卷或医生验证的 URTI； 事实上，医生验证的 URTI 的有效性受到审查。 17 在报告 URTI 症状的运动员中进行病原体检测的少数研究，9, 17 并与久坐的对照组进行比较，9 表明只有大约三分之一的 URTI 报告是 由于呼吸道病原体。9, 17 这种在有 URTI 症状的运动员中呼吸道病原体检测率相当低 (~30%)9, 17 似乎与人类鼻病毒导致 80% 的成年人自我诊断普通感冒的证据不一致。 季节性秋季高峰。19 这种差异可能是因为对运动员的研究是在全年 17 或在南半球夏季 9 期间进行的，那时普通感冒发病率低，过敏发病率高。 然而，这些研究强调，自我报告或医生验证的 URTI 不应普遍被称为具有传染性。 9, 17 也许最有说服力的是，与运动员相比，运动员中患有病原体鉴定的 URTI 的比例并不低 (29%) 与久坐的对照组 (22%) 相同。9 因此，这些发现并不支持运动员比非运动员更容易受到非传染性起源（例如，炎症和过敏）的 URTI 症状的观点。 一项针对参加伦敦马拉松的 208 名休闲跑步者的研究表明，赛后自我报告的 URTI 症状与通过问卷评估的过敏症之间存在关联，而且跑步者的过敏发生率高于对照组。 18 这些有趣的发现需要在一项比较运动员和 使用金标准皮肤点刺测试和特定 IgE 测试作为过敏问卷的非运动员表现出较差的敏感性 (58%)。 18 显然，解决这一争议代表了未来研究的富有成果的途径，其结果可能会指导预防策略 和治疗。 还需要未来的研究来验证和阐明最近对 236 名运动员进行的一项研究的结果，该研究表明先前同时感染巨细胞病毒和爱泼斯坦巴尔病毒（N=50）导致冬季 URTI 发作减少 50%，作者建议的这一发现代表 20 无论 URTI 症状的原因是什么（感染性或非感染性），专家们普遍同意自我报告的 URTI 会阻碍大量运动训练，10 但有些令人惊讶的是，人们对运动表现的影响知之甚少 .21 迫切需要适当设计的研究来解开传染性和非传染性 URTI 症状及其对运动表现的影响。

 运动和免疫：我们知道什么，我们还需要学习什么？

 众所周知，急性和慢性运动会改变粘膜免疫3 以及先天免疫系统（例如中性粒细胞、单核细胞和自然杀伤细胞）和获得性免疫系统（T 和 B 淋巴细胞）的循环细胞的数量和功能。 6 例如，T 细胞和 B 细胞功能似乎对训练有素的运动员的训练负荷增加很敏感，1 型 T 细胞的循环数量减少，T 细胞增殖反应减少，受刺激的 B 细胞减少 Ig 合成。6 为了全面回顾研究运动对免疫影响的文献，读者可以参考 ISEI（国际运动和免疫学学会）的立场声明。6 此外，免疫的神经内分泌调节（ 例如，通过糖皮质激素）应对压力源（如运动）最近由 Dhabhar 进行了审查。 22 在这里，我们将对我们认为重要的近期广告提供评论 将指导未来研究工作与训练有素的运动员的免疫研究具有特定相关性的持续存在的争议和持续的争议：短期适度体育活动的抗炎健康益处在本专题的其他地方进行了讨论。 尽管免疫系统的先天性和获得性分支之间的区别有些粗略，并且我们认识到它们是密不可分的（例如，通过先天性免疫系统在抗原呈递中的作用），但在这里我们将首先关注先天性，然后是获得性 细胞成分。

 运动与先天免疫

 知识上的主要差距之一，也是持续研究工作的一个关键挑战，仍然是观察到的运动员急性和慢性运动（通常为 15-25%）的先天或获得性免疫变化是否会改变宿主防御和疾病易感性。 6 由于可能与成本、伦理和可及性相关的禁止性原因，很少有研究监测临床相关的免疫措施并对一个赛季的高水平运动员（和对照组）的 URTI 进行平行评估； 因此，评论员只能猜测运动员免疫力和感染之间的因果关系。 例如，Hellard 等人 11 优雅地证明，在训练负荷增加约 10% 的情况下，优秀游泳运动员患上 URTI 的风险增加约 10%，但未对免疫功能进行测量。 最近的一项研究表明，跑步者和骑自行车者进行为期 3 天的功能性过度锻炼后，在恢复后的 14 小时和 38 小时内，粒细胞和单核细胞的吞噬作用和氧化爆发活性降低，但并未将随后期间的 URTI 发生率与对照组进行比较。 23 专家一致认为，急性运动和训练对树突状细胞 (DC) 的影响仍然知之甚少，这是一个成熟的研究课题，特别是考虑到 DC 在通过向 T 和 B 细胞呈递抗原和共刺激分子来启动适应性免疫反应方面的关键作用。 6 急性运动已被证明会增加循环髓样和浆细胞样 DCs 的数量，24 并且最近的工作表明，急性最大运动量增加了单核细胞衍生 DCs 的离体生成，25 但这些观察结果的功能后果仍然知之甚少。

 运动和获得性免疫

 鉴于幼稚 T 细胞在宿主防御新病原体和感染易感性方面的重要作用，现在认为在剧烈运动后优先动员衰老的 T 细胞进入循环可促进细胞凋亡并为新功能的 T 细胞腾出空间，即运动扩大 26 最近的研究表明，高水平耐力训练可能会导致 T 细胞区室过早发生与年龄相关的变化，即胸腺输出减少，评估为低信号联合 T 细胞受体切除圈水平 运动员循环 T 细胞与年龄匹配对照的差异。 27 最近的另一项研究表明，在训练有素的男性自行车手中进行 1 周的强化训练会损害运动后初始 CD8+ T 淋巴细胞 (CD27+CD45RA+) 和细胞毒性 T 淋巴细胞从血液中的流出。 28 作者认为，强化训练后对运动的较小神经内分泌反应（减少血浆肾上腺素和皮质醇）可能 解释他们的发现，他们认为这表明免疫监视减少。 初步工作表明，性可能会减轻运动对 T 细胞重新分布的影响，29 以及其他免疫措施（在别处进行了审查），30 但未来的工作需要阐明性激素的作用。 最近的一项研究表明，耐力运动员的高训练负荷与循环调节性 T 细胞 (CD4+CD25+CD127low/−) 的静息水平更高和全血抗原刺激的白细胞介素 10 产生更多有关。 31 在另一项研究中， 同一作者还表明，每周进行大量体力活动（每周⩾ 7 小时）的个体提高了全血抗原刺激的白细胞介素 10 的产生，并且在冬季的几个月里，URTIs 的发生率是那些锻炼 3 小时的个体的两倍多。 –6 h 每周。32 矛盾的是，这些免疫调节反应可能会削弱对新病原体的免疫反应（增加 URTI 发生率）并抑制抗肿瘤免疫，22 但增强的抗炎状态的长期影响被认为是有益的 对抗轻度炎症和心血管疾病、2 型糖尿病、肥胖症和癌症的相关风险。 32

 展望未来，在可行的情况下，鼓励运动免疫学家使用体内免疫方法。 通过在正常组织环境中启动整合和高度协调的免疫反应，体内免疫方法提供了更多临床相关信息，超出了体外测定的范围。 33 许多体外测定的弱点是需要将免疫细胞与其正常环境分离 并在人工培养中孵化。 体内免疫方法的例子包括评估对流感疫苗接种的循环抗体反应 34 和对皮内抗原（延迟型超敏反应）或局部应用抗原（接触超敏反应）的局部皮肤反应。6, 33 与急性应激诱导免疫 - 增强假说，22 研究表明，在免疫力欠佳的人群（例如老年人）或抗原免疫原性较低的人群中，运动可以提高流感疫苗接种的成功率（循环抗体滴度）； 但对于高水平培训对流感疫苗接种成功的影响知之甚少。34 这种方法的公认局限性包括，与循环抗体滴度相比，流感疫苗接种的离体 T 细胞反应与疫苗保护的相关性更强。 .34 此外，流感疫苗中加入重复抗原会引发一级、二级和三级抗体反应的混合。6 使用新抗原提供了评估运动压力对新免疫反应诱导和三级抗体影响的机会。 召回先前发展的免疫力。 我们最近使用皮肤接触敏化剂二苯基环丙烯酮 (DPCP) 进行的研究表明，跑步机以 60% V̇O2peak 运行 2 小时会降低 T 细胞介导的免疫的诱导（-67%：图 1a）和回忆反应（-19%： 图 1d)35 在重复每月暴露后在皮肤对 DPCP 的反应中达到可重现的高原的受试者中（图 1c）。 我们显示长时间中等强度运动对皮肤对刺激性巴豆油的反应没有影响（图 1b）表明细胞介导的免疫受到抑制。 这些数据也挑战了短期、高强度耐力运动会降低免疫力的概念，因为在 80% V̇O2peak 下跑步 30 分钟不会影响对 DPCP 的免疫诱导（图 1a）。 这些研究结果支持以下建议：运动员应考虑用较短的峰值训练代替一些长时间、中等强度的训练，以限制训练引起的免疫损伤（表 1）。7 这项工作也可能有助于解释 URTI 症状减轻的原因 在总体训练量减少但强度仍然很高的逐渐减少期间，高水平游泳运动员中。 11 鉴于 DPCP 是良性的，确定特定于感染（皮肤和其他）的反应的临床意义是未来的重要途径 研究。 优选地，皮肤对 DPCP 的回忆反应的强度可以推广到皮肤免疫之外，以表明免疫系统对感染性挑战做出反应的一般能力，但这需要调查。

 环境压力、URTI 和免疫功能：我们知道什么，我们还需要学习什么？

 在常规训练和比赛期间，许多运动员经历劳力性高热（核心温度 >39.5 °C）、脱水、外周变冷和中度海拔或缺氧（高达 ~2500 米）。36, 37 运动员还暴露于训练之外的环境压力 . 例如，在精英运动员常见的长途航空旅行中，机舱内的低压缺氧使运动员暴露于相当于 1800–2400 米的海拔。38 一些运动员还经历了更极端的热应激，例如劳力性热病 伤亡（核心温度可以 >41 °C）和体温过低（核心温度 <35 °C，例如，开放水域游泳运动员）和高海拔（高达 5000 米）在参加冒险比赛或间歇性缺氧的运动员中经历过 训练。 在炎热、寒冷和高海拔环境中，运动表现通常会下降，但也有明显的例外，例如在高海拔地区提高短跑和跳跃能力 36 以及在凉爽环境中提高耐力运动表现。 39 由于在极端环境中锻炼会增加对运动的要求 中枢神经系统、心血管系统和新陈代谢。 身体对运动、热应激或缺氧挑战的反应由中枢神经系统和下丘脑-垂体-肾上腺轴和交感神经-肾上腺-髓质轴的效应肢发起和协调，产生免疫调节激素，如皮质醇、肾上腺素 22 因此，很容易理解为什么在 1990 年代后期，该领域的先驱之一 Roy Shephard 博士假设在不利的环境中锻炼，其刻板的应激激素反应超出了在有利条件下锻炼时所见， 可能会对免疫功能和宿主防御造成更大的破坏。8 有关调查环境压力对免疫影响的早期研究的详细讨论，请读者参阅 ISEI 立场声明和早期评论。7、8、40 在这里，我们将提供评论 关于我们认为将指导未来研究的重要最新进展和持续争议 在可能的情况下，ch 致力于研究在常见环境（例如，-10 到 40 °C 的气温和 <2500 米海拔）中锻炼或训练的运动员。

 热应力和免疫力

 一项持续存在的争议涉及在炎热或寒冷的环境中锻炼或休息是否对运动员的免疫健康有害。 核心温度保持在正常基线的 2 °C 以内的实验室研究表明，热环境或冷环境对免疫功能的影响相当有限，但据报道 T 细胞介导的免疫可能会降低（表 2）。 41, 42 因此，大多数现有证据不支持在炎热或寒冷的条件下锻炼对免疫功能构成更大威胁的论点，与热中性条件相比。 7 值得注意的是，在炎热（与凉爽）条件下锻炼的个体 往往会更快疲劳或降低工作速度，因此他们在高温下承受的运动压力往往是自限性的。 最近在运动免疫学和运动生理学中，由于剧烈训练或高温比赛导致的适度脱水（通常体重减少 1-4%）已成为关注的焦点。 一些运动免疫学家认为，脱水可能会损害运动员的免疫健康，因为脱水会增加生理压力和免疫调节应激激素。 43 尽管最近的证据表明适度脱水可能会暂时降低粘膜免疫，44 压倒性的证据表明适度脱水 运动员通常经历的对运动免疫反应的影响相对有限（表 2）。45, 46, 47 例如，最近的研究表明，由液体限制和长时间中等强度运动引起的适度脱水（约 4% 的体重减轻） 不影响循环抗原刺激的细胞因子产生、泪液 IgA 或唾液抗菌反应，包括 IgA、溶菌酶和乳铁蛋白。​​ 45, 46, 47 这些最近的运动免疫学发现与当前运动生理学研究的结果一致，这些研究挑战了广泛持有的信念 适度脱水会降低运动表现 e 在高温中。48 一个持续研究兴趣的领域，也是最近一篇综述的主题，49 重点关注免疫失调和炎症与热耐受改变、劳累性热病和中暑的假定关系。7 最近的研究表明， 对肌肉损伤性运动的炎症反应（循环白细胞介素 6 增加，一种已知的热原）与 30 分钟后运动热应激期间核心温度的随后升高呈正相关（r = 0.67）。 50 虽然增强的炎症反应可能会增加 热应激和急性运动热应激期间热病的风险，最近的研究指出炎症在获得性细胞热耐受性中的重要作用（例如，热休克蛋白 70 的细胞保护作用）和与热相关的更慢性的表型适应 适应。51 研究可以更好地了解获得性细胞热耐受性及其在 th 中的拟议作用。 非常需要热适应的调节适应。 正如调查普遍认为经常接触桑拿会降低 URTI 发病率的研究一样。 52

 尽管并非完全定论，但有证据表明，寒冷暴露通常先于 URTIs，包括“普通感冒”53 的发病率增加。 通过冷却皮肤而“发冷”会导致“普通感冒”。 尽管这些观点存在争议，但一些证据表明，鼻子和上呼吸道（甚至脚）的外周冷却可以增加普通感冒症状，这可能是通过抑制免疫细胞运输并为病毒复制创造合适的局部环境来实现的。 54 有些矛盾 是另一组的研究结果表明，频繁的冷水浸泡具有轻微的免疫刺激作用。 55 尽管最近有人质疑冷冻疗法对训练适应的好处，56 冷水浸泡或冷空气暴露形式的运动后冷冻疗法已变得流行 增加运动训练和比赛方案； 因此，这些做法对免疫和宿主防御的影响需要调查。

 海拔压力和免疫力

 海拔训练通常涉及运动员被动暴露或在缺氧条件下锻炼，每天 1-6 小时，持续 5-14 天。 尽管对运动表现的好处一直存在争论，57, 58 关于各种高原训练方法如何影响运动员的免疫力和宿主防御的讨论和研究相对较少。 这是令人担忧的，因为目前的共识是，海拔和低氧暴露会降低体内和体外细胞介导的免疫功能，并增加自我报告的呼吸道感染（表 2）38、59、60、61、62、63、64， 65, 66：即使仅考虑涉及高水平运动员的研究，情况仍然如此（表 3）。 59, 60, 64 然而，在解释自我报告的高原 URTI 研究结果时需要谨慎，因为存在相当大的重叠 63 文献中出现的一个新趋势是，在运动员完成高海拔训练或高海拔训练低海拔训练方法的研究中，免疫力和宿主防御通常会降低59、60 , 61, 64 但不是在涉及间歇性缺氧训练的研究中。 67, 68, 69 最近使用间歇性缺氧训练的研究实际上描述了免疫措施的有利结果，包括减少循环衰老 T 淋巴细胞亚群 68 和增加的粘膜免疫 69； 尽管存在局限性，但其中一些研究是在未受过训练的个体中进行的。 由于现在正在使用多种形式的缺氧训练，57 未来的研究应设法确定这些高原训练方法中的每一种如何影响运动员的免疫功能和 URTI 发生率。

 运动免疫学领域的未来研究方向

 未来的研究应该解开高水平运动员免疫力下降和宿主防御能力下降的心理社会和生理基础。 鉴于心理压力对免疫功能的影响众所周知，22 可以想象，高水平运动员的心理社会压力状态（与生活压力、合同问题、团队选择、受伤、旅行、睡眠中断、时差等有关） ) 至少部分说明了上述改变或调节运动对免疫和宿主防御的影响。 最近的一项研究中有趣的观察结果表明，报告高压力但不低压力的男性通过定期锻炼会降低 URTI 发病率，这支持了这一概念。 12 这和“压力反应性”70 的概念，假设对压力的夸大和减弱反应都会增加 患病风险仍然是需要调查的成熟话题。 通过与不断扩大的心理神经免疫学领域的专家合作，运动免疫学家可以在不久的将来运用他们的才能来回答这些重要问题。

 最后，运动科学家可以使用丰富多样的工具包来评估训练适应性，而不是评估适应不良和免疫抑制。 因此，运动免疫学家应继续寻求确定可用于此目的的可用于现场的非侵入性免疫标志物。 我们最近证明，泪液分泌型 IgA 具有作为粘膜免疫和普通感冒风险的非侵入性生物标志物的潜力，因为在个人报告普通感冒季节期间出现 URTI 症状前一周，泪液分泌型 IgA 水平下降（图 2）。45 研究很重要，不仅因为泪液很容易获得，还因为据估计高达 95% 的感染是从粘膜表面开始的。 71 纳米技术和微流体的进一步发展可能在不久的将来为 现场泪液测量装置和隐形眼镜的连续生物监测。

 利益冲突

 作者宣称没有利益冲突。

 长时间的中等强度运动会损害人体细胞介导的体内免疫反应的诱导和诱发阶段。 （ a ）在用 DPCP 诱导接触超敏反应之前的运动压力对 28 天后皮肤增厚对攻击的反应的影响。 显示的是休息对照组（CON）； 30 min 在 60% V̇O2peak (30MI); 在 80% V̇O2peak (30HI) 时为 30 分钟，在 60% V̇O2peak (120MI) 时为 120 分钟。 (b) 坐姿休息 (CON) 或长时间运动压力 (120MI) 对巴豆油刺激性刺激引起的皮肤发红反应的影响（图 a 和 b 改​​编自 Diment 等人 33）。 (c) 每月重复暴露 DPCP 4 个月可促进皮肤增厚反应以达到稳定状态。 (d) 长时间运动压力 (120MI) 对 DPCP 诱发反应的影响，参与者在每月接触 DPCP 4 个月后，皮肤对 DPCP 的反应达到平台期（图 c 和 d 改编自 Harper Smith 等人 35）。 #P<0.05 对比 CON。 * P<0.05 与上个月的挑战相比。 数据是平均值±sd。

Figure 1

Prolonged moderate intensity exercise impairs both the induction and elicitation phases of the cell-mediated in vivo immune response in humans. (a) Effect of exercise stress prior to induction of contact hypersensitivity with DPCP on skin thickening response to challenge 28 days later. Shown are rested control group (CON); 30 min at 60% V̇O2peak (30MI); 30 min at 80% V̇O2peak (30HI) and 120 min at 60% V̇O2peak (120MI). (b) Effect of seated rest (CON) or prolonged exercise stress (120MI) on skin redness response to irritant challenge with croton oil (Panels a and b are adapted from Diment et al.33). (c) Repeated monthly DPCP exposures for 4 months boosts the skin thickening response to achieve a plateau. (d) Effect of prolonged exercise stress (120MI) on elicitation response to DPCP in participants who reached a plateaux in skin response to DPCP after monthly exposures for 4 months (Panel c and d are adapted from Harper Smith et al.35). #P<0.05 vs CON. *P<0.05 vs previous month challenge. Data are mean±s.d.

Figure 2

Tear fluid SIgA concentration (a) and secretion rate (b) in the week prior to onset of upper respiratory symptoms (PRE URS) and >3 weeks following URS (RECOVERY) during the common cold season. Mean±s.e.m. *P<0.05 tear SIgA lower PRE URS vs RECOVERY. Adapted from Hanstock et al.45

Table 1. Suggested strategies for modifying training and recovery activities to limit the risk of training-induced impairments in immune health

Training descriptor	Comment and evidence where available
Frequency	Increase the frequency of shorter training sessions rather than enduring fewer but longer sessions.11
Volume	Reduce the overall weekly training volume and/or volume of individual training sessions.11
Intensity	Avoid prolonged intensive training sessions or activities. Employ shorter sharper (spike) sessions mixed with lower-intensity work.11, 33
Load (volume × intensity)	Systematically manipulate either the training volume and/or intensity to manage the degree of training load.11
Load increments	Reduce the size of increments in frequency, volume, intensity and load of training, for example, increases of 5–10% per week rather than 15–30%.11
Load sequencing—weekly microcycle	Undertake two or three easy–moderate training sessions after each high-intensity session rather than the traditional pattern of simply alternating hard–easy sessions.
Load sequencing—multi-week macrocyle	Plan an easier recovery or adaptation week every second or third week rather than using longer 3–6-week cycles with increasing loads.
Recovery—session per week	Implement recovery activities immediately after the most intensive or exhaustive training sessions.
Recovery—season	Permit athletes at heightened risk of illness (for example, those with recent illness episode)11 a longer period of passive and active recovery (several weeks) after periods of intensified training.

• Adapted from Walsh et al.