运动对免疫系统的影响.doc

Position Statement
Part one: Immune function and exercise
Neil P.Walsh1, Michael Gleeson2, Roy J. Shephard3, Maree Gleeson4 Jeffrey
A.Woods5, Nicolette C. Bishop2, Monika Fleshner6, Charlotte Green7, Bente
K. Pedersen7, Laurie Hoffman-Goetz8, Connie J. Rogers9, Hinnak
Northoff10, Asghar Abbasi10, Perikles Simon11
11 School of Sport, Health and Exercise Sciences, Bangor University, UK.
12 School of Sport, Exercise and Health Sciences, Loughborough University, UK.
13 Faculty of Physical Education and Health, University of Toronto, Canada.
14 Hunter Medical Research Institute and Faculty of Health, University of
Newcastle, Australia.
15 Department of Kinesiology and Community Health, University of Illinois at
Urbana-Champaign, USA.
16 Department of Integrative Physiology, University of Colorado, USA.
17 The Centre of Inflammation and Metabolism at the Department of Infectious
Diseases, and Copenhagen Muscle Research Centre, Rigshospitalet, the
Faculty of Health Sciences, University of Copenhagen, Denmark.
18 Department of Health Studies and Gerontology, University ofWaterloo, Canada.
19 Department of Nutritional Sciences, Pennsylvania State University, USA.
10 Institute of Clinical and Experimental Transfusion Medicine, University of
Tuebingen, Germany.
11 Department of Sports Medicine, Disease Prevention and Rehabilitation,
Johannes Gutenberg-University Mainz, Germany.
CONSENSUS 共识STATEMENT陈述
An ever-growing不断增长的 volume量 of peer-reviewed同行评审 publications 出版物speaks to the recent and rapid growth in both scope规模、 范围and understanding理解 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国际运动免疫协会 and Immunology (ISEI) in 1989 (ISI Web of KnowledgeSM). We recognise承认 the epidemiological流行病学distinction 区别between the generic term 通用术语“physical activity” 体力活动and the specific category类 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 影响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.
In this position statement, a panel of world-leading experts provides a consensus of
current knowledge, briefly covering the background, explaining what we think we
6 • Immune function and exercise
EIR 17 2011 - position statement part 1
Correspondence:
NeilWalsh; email: [e-mail]; telephone: [phone]
know with some degree of certainty, exploring continued controversies, and pointing
to likely directions for future research. Part one of this position statement focuses
on ‘immune function and exercise’ and part two on ‘maintaining immune
health’. Part one provides a brief introduction and history (Roy Shephard) followed
by sections on: respiratory infections and exercise (Maree Gleeson); cellular细胞的 innate固有的immune function and exercise (Jeffrey Woods); acquired immunity and exercise
(Nicolette Bishop); mucosal粘膜 immunity and exercise (Michael Gleeson and Nicolette
Bishop); immunological 免疫学的methods in exercise immunology (Monika Fleshner);
anti-inflammatory effects of physical activity (Charlotte Green and Bente Pedersen);
exercise and cancer (Laurie Hoffman-Goetz and Connie Rogers) and finally,
“omics” in exercise (Hinnak Northoff, Asghar Abbasi and Perikles Simon).
The focus on respiratory infections in exercise has been stimulated 刺激by the commonly
held beliefs that the frequency of upper respiratory tract infections (URTI)
is increased in elite endurance精英耐力 athletes after single bouts较量 of ultra-endurance exercise and during periods of intensive training. The evidence to support these concepts
is inconclusive尚无定论, but supports the idea that exercised-induced immune suppression抑制 increases susceptibility易感性 to symptoms of infection, particularly around the
time of competition, and that upper respiratory symptoms are associated with performance
decrements递减. Conclusions from the debate on whether sore throats are
actually caused by infections or are a reflection of other inflammatory stimuli刺激
associated with exercise remains unclear.
It is widely accepted that acute and chronic exercise alter the number and function of
Circulating循环 cells of the innate immune system (e.g. neutrophils嗜中性粒细胞, monocytes 单核细胞and natural killer (NK) cells). A limited number of animal studies has helped us determine the extent to which these changes alter susceptibility to herpes simplex and influenza virus infection. Unfortunately, we have only ‘scratched the surface’ regarding关于
whether exercise-induced changes in innate immune function alter infectious disease
susceptibility or outcome and whether the purported声称 anti-inflammatory effect
of regular exercise is mediated 导through exercise-induced effects on innate immune
cells.We need to know whether exercise alters migration of innate cells and whether
this alters disease susceptibility. Although studies in humans have shed light on
monocytes单核细胞, these cells are relatively immature and may not reflect the effects of
exercise on fully differentiated tissue macrophages巨噬细胞. Currently, there is very little
information on the effects of exercise on dendritic 树突状cells, which is unfortunate given
the powerful influence of these cells in the initiation of immune responses.
It is agreed that a lymphocytosis淋巴细胞 is observed during and immediately after exercise,
Proportional比例 to exercise intensity and duration, with numbers of cells (T
cells and to a lesser extent B cells) falling below pre-exercise levels during the
early stages of recovery, before returning to resting values normally within 24 h.
Mobilization动员 of T and B cell subsets in this way is largely influenced by the
actions of catecholamines儿茶酚胺. Evidence indicates that acute exercise stimulates T cell
subset activation 激活in vivo and in response to mitogen有丝分裂原- and antigen-stimulation抗原刺激.Although numerous studies report decreased mitogen- and antigen-stimulated T
cell proliferation following acute exercise, the interpretation of these findings
may be confounded by alterations in the relative proportion of cells (e.g. T, B and
Immune function and exercise • 7
EIR 17 2011 - position statement part 1
NK cells) in the circulation that can respond to stimulation. Longitudinal纵向 training
studies in previously sedentary people have failed to show marked changes in T and
B cell functions provided that blood samples were taken at least 24 h after the last
exercise bout. In contrast, 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.
The cause of this apparent depression in acquired immunity appears to be related
to elevated circulating stress hormones, and alterations in the pro/anti-inflammatory
cytokine balance in response to exercise. The clinical significance of these changes
in acquired immunity with acute exercise and training remains unknown.
The production of secretory immunoglobulin A (SIgA) is the major effector function
of the mucosal immune system providing the ‘first line of defence’ against
pathogens. To date, the majority of exercise studies have assessed saliva SIgA as a
marker of mucosal immunity, but more recently the importance of other antimicrobial
proteins in saliva (e.g. á-amylase, lactoferrin and lysozyme) has gained
greater recognition. Acute bouts of moderate exercise have little impact on
mucosal immunity but prolonged exercise and intensified training can evoke
decreases in saliva secretion of SIgA. Mechanisms underlying the alterations in
mucosal immunity with acute exercise are probably largely related to the activation
of the sympathetic nervous system and its associated effects on salivary protein
exocytosis and IgA transcytosis. Depressed secretion of SIgA into saliva during
periods of intensified training and chronic stress are likely linked to altered
activity of the hypothalamic-pituitary-adrenal axis, with inhibitory effects on IgA
synthesis and/or transcytosis. Consensus exists that reduced levels of saliva SIgA
are associated with increased risk of URTI during heavy training.
An important question for exercise immunologists remains: how does one measure
immune function in a meaningful way? One approach to assessing immune function
that extends beyond blood or salivary measures involves challenging study participants
with antigenic stimuli and assessing relevant antigen-driven responses including
antigen specific cell-mediated delayed type hypersensitivity responses, or circulating
antibody responses. Investigators can inject novel antigens such as keyhole
limpet haemocyanin (KLH) to assess development of a primary antibody response
(albeit only once) or previously seen antigens such as influenza, where the subsequent
antibody response reflects a somewhat more variable mixture of primary, secondary
and tertiary responses. Using a novel antigen has the advantage that the investigator
can identify the effects of exercise stress on the unique cellular events required for a
primary response that using a previously seen antigen (e.g. influenza) does not permit.
The results of exercise studies using these approaches indicate that an acute bout
of intense exercise suppresses antibody production (e.g. anti-KLH Ig) whereas moderate
exercise training can restore optimal antibody responses in the face of stressors
and ageing. Because immune function is critical to host survival, the system has
evolved a large safety net and redundancy such that it is difficult to determine how
much immune function must be lost or gained to reveal changes in host disease susceptibility.
There are numerous examples where exercise alters measures of immunity
by 15-25%.Whether changes of this magnitude are sufficient to alter host defence,
disease susceptibility or severity remains debatable.
8 • Immune function and exercise
EIR 17 2011 - position statement part 1
Chronic inflammation is involved in the pathogenesis发病 of insulin resistance, atherosclerosis,neurodegeneration, and tumour growth. Evidence suggests that the prophylactic effect of exercise may, to some extent, be ascribed to the anti-inflammatory
effect of regular exercise mediated via a reduction in visceral fat mass and/or by
induction of an anti-inflammatory environment with each bout of exercise (e.g. via
increases in circulating anti-inflammatory cytokines including interleukin (IL)-1
receptor antagonist and IL-10). To understand the mechanism(s) of the protective,
anti-inflammatory effect of exercise fully, we need to focus on the nature of exercise
that is most efficient at allieviating the effects of chronic inflammation in disease.
The beneficial effects of endurance exercise are well known; however, the antiinflammatory
role of strength training exercises are poorly defined. In addition, the
independent contribution of an exercise-induced reduction in visceral fat versus
other exercise-induced anti-inflammatory mechanisms needs to be understood better.
There is consensus that exercise training protects against some types of cancers.
Training also enhances aspects of anti-tumour immunity and reduces inflammatory
mediators. However, the evidence linking immunological and inflammatory mechanisms,
physical activity, and cancer risk reduction remains tentative.
In the very near future, genomics, proteomics, and metabolomics may help exercise
immunologists to better understand mechanisms related to exercise-induced
modulation of the immune system and prevention (or reduced risk) of diseases by
exercise training. In addition, these technologies might be used as a tool for optimizing
individual training programmes. However, more rigorous standardization
of procedures and further technological advances are required before practical
application of these technologies becomes possible.
Key Words: exercise; sport; training; immune; pathogen; infection; innate;
acquired; mucosal; saliva; leukocyte; monocyte; neutrophil; granulocyte; lymphocyte;
immunoglobulin; method; cytokine; interleukin; inflammation; cancer;
genomics; proteomics; metabolomics
INTRODUCTION AND HISTORY
Two recent papers have summarized the scientific history of exercise immunology
(263) and its development as a specific discipline (264) with its own international
society and a dedicated journal. Exercise immunology has quite a short history
relative to many branches of the exercise sciences, the modern era of careful epidemiological
investigations and precise laboratory studies beginning in the mid
1980s. However, an ever-growing volume of peer-reviewed publications speaks to
a rapid growth in both scope and understanding of the topic since that date. In
addition to enquiries into many areas of intrinsic scientific interest, exercise immunologists
have found diverse applications for their talents in augmenting population
health and maintaining high performance athletes in peak physical condition.
From early during the 20th century, clinicians had pointed to what seemed adverse
effects of prolonged heavy exercise upon both resistance to and the course of various
viral and bacterial diseases (25, 261). These concerns were seemingly sub-
Immune function and exercise • 9
EIR 17 2011 - position statement part 1
stantiated by a 2-6 fold increase in the reported symptoms of upper respiratory
infection (URTI) for several weeks following participation in marathon or ultramarathon
events (200, 224). The influence of exercise on the risks of URTI is discussed
in the following section. A transient fall in the circulating natural killer
(NK) cell count following a sustained bout of vigorous exercise (270) seemed to
offer a mechanism explaining the increase in risk; the temporary lack of NK cells
and killer cell activity offered an “open window,” a period when a reduced resistance
to viral infections allowed easier access to infecting micro-organisms. Innate immunity
is discussed in detail later in this part of the position statement. In one report,
the reduction in NK cell count persisted for seven days following exercise (259), but
in most studies, circulating NK cell numbers and activity have been described as
being depressed for only a few hours, raising doubts as to whether the “window”
was open long enough to account for the increased vulnerability to infection. Moreover,
technical advances (particularly in automated cell counting and identification)
(85) have underlined that