Immune Function in Sport and Exercise: Advances in Sport and Exercise Science Series

321 Pages·2006·8.22 MB·English

by  Connell Neil

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First published 2006
ISBN 0 443 10118 3
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vii
Contributors
Michael Gleeson BSc PhD
Professor of Exercise Biochemistry, School of Sport and Exercise Sciences,
Loughborough University, Loughborough, UK
Nicolette C. Bishop BSc PhD
Lecturer in Exercise Physiology, School of Sport and Exercise Sciences,
Loughborough University, Loughborough, UK
Andrew K. BlanninBSc PhD
Lecturer, School of Sport and Exercise Sciences, University of Birmingham,
Birmingham, UK
Victoria E. Burns BSc PhD
Research Fellow, School of Sport and Exercise Sciences, University of
Birmingham, Birmingham, UK
Graeme I. Lancaster BSc MSc PhD
Post-doctoral Researcher, School of Medical Sciences, Division of Biosciences,
RMIT University, Bundoora, Melbourne, Victoria, Australia
Paula Robson-Ansley BSc PhD
Senior Lecturer, Department of Sport and Exercise Science, University of
Portsmouth, Portsmouth, UK
Neil P. Walsh BSc MSc PhD
Lecturer in Physiology, School of Sport, Health and Exercise Sciences, University
of Wales, Bangor, UK
Martin WhithamBSc PhD
Lecturer in Exercise Physiology, School of Sport, Health and Exercise Sciences,
University of Wales, Bangor, UK
ix
Foreword
When I conducted my first exercise immunology study in 1984 very little was known
about the influence of exercise on immune function. Only a few other investigators,
notably Pedersen, Mackinnon and Hoffman-Goetz were conducting exercise
immunology studies during the mid-1980s (Pedersen et al 1988, Mackinnon 1986,
Hoffman-Goetz et al 1986).
My interest in the immunology of exercise was spurred by a brief review article
published in the 1984 Olympic issue of the Journal of the American Medical Association
(Simon 1984). In this report Simon urged that ‘there is no clear experimental or clin-
ical evidence that exercise will alter the frequency or severity of human infections’.
This opinion did not coincide with my experience as a marathon athlete. During
hard periods of training and after marathon race events I periodically experienced
sore throats or sickness and observed the same in other marathoners. On the other
hand, during training of normal intensity, I seldom experienced sickness and later
observed in a series of surveys with hundreds of athletes that 8 out of 10 runners
reported the same experience.
I located a clinical immunology researcher (Nehlsen-Cannarella) who was also
interested in exercise influences on immunity, and initiated a series of studies that
have now spanned two decades. Along the way we have examined immune
responses to the entire continuum of exercise workloads (one-minute Wingate tests
through 30-minute brisk walks to 27-hour ultramarathons) in all age groups (includ-
ing children and the elderly) and fitness levels (from morbidly obese women to
Olympic female rowers). We have learned so much, and a list of key findings from
my research team and others is as follows:
● Moderate exercise (30-45 minutes’ brisk walking, 5 days per week) produces
favourable immune changes that decrease the number of sick days in both young
and old adults by 25-50% compared to randomized sedentary controls. This is by
far, in my opinion, the most important finding that has emerged from exercise
immunology studies during the past two decades, and is consistent with public health
recommendations urging people to engage in 30 minutes or more of near-daily physical
activity.
● Many components of the immune system exhibit adverse change after prolonged,
heavy exertion lasting longer than 90 minutes. These immune changes occur in
several compartments of the immune system and body (e.g. the skin, upper res-
piratory tract mucosal tissue, lung, blood and muscle). During this ‘open win-
dow’ of impaired immunity (which appears to last between 3 and 72 hours,
depending on the immune measure), viruses and bacteria may gain a foothold,
increasing the risk of subclinical and clinical infection.
x FOREWORD
● During and after heavy and intensive exercise workloads, individuals experience
a sustained neutrophilia and lymphocytopenia. Of all immune cells, natural killer
(NK) cells, neutrophils and macrophages (all of the innate immune system) are
the most responsive to the effects of acute exercise, both in terms of numbers and
function. The longer and more intense the exercise bout (e.g. competitive marathon
races), the greater and more prolonged the response, with moderate exercise bouts
(<60% maximal oxygen uptake and <45 minutes’ duration) evoking relatively little
change from resting levels. Many mechanisms appear to be involved including
exercise-induced changes in stress hormone and cytokine concentrations, body
temperature changes, increases in blood flow and dehydration.
● Of the various nutritional countermeasures to exercise-induced immune pertur-
bations that have been evaluated thus far, ingestion of carbohydrate beverages
during intense and prolonged exercise has emerged as the most effective.
However, although carbohydrate supplementation during exercise decreases
exercise-induced increases in plasma cytokines and stress hormones, it is largely
ineffective in preventing falls in the function of some immune system compon-
ents including NK cells and T lymphocytes. Other nutritional countermeasures
such as glutamine and antioxidant supplements have had disappointing results
and thus the search for others continues.
● As individuals age, they experience a decline in most cell mediated and humoral
immune responses. Agrowing number of studies indicate that immune function
is enhanced in conditioned versus sedentary elderly subjects and that exercise
training improves antibody responses to vaccines and other aspects of immuno-
surveillance.
The future of exercise immunology is in determining whether or not exercise-
induced perturbations in immunity help explain improvements in other clinical out-
comes such as cancer, heart disease, type 2 diabetes, arthritis and other chronic
diseases. This is an exciting new area of scientific endeavour and preliminary data
suggest that immune changes during exercise training are one of multiple mecha-
nistic factors. For example, type 2 diabetes and cardiovascular disease are associ-
ated with chronic low-grade systemic inflammation. During exercise, interleukin
(IL)-6 is produced by muscle fibres and stimulates the appearance in the circulation
of other anti-inflammatory ctyokines such as IL-1 receptor antagonist and IL-10.
IL-6 also inhibits the production of the proinflammatory cytokine tumour necrosis
factor (TNF)-αand stimulates lipolysis and fat oxidation. With weight loss from energy
restriction and exercise, plasma levels of IL-6 fall, skeletal muscle TNF-α decreases
and insulin sensitivity improves. Thus, IL-6 release from the exercising muscle may
help mediate some of the health benefits of exercise including metabolic control of
type 2 diabetes (Petersen & Pedersen 2005). The exercise-induced cytokine links
between adipose and muscle tissues clearly warrant further study. It is my belief
that most of the established health benefits of regular physical activity have a stronger
linkage to immune alterations than has previously been suspected.
Thus, during the past 20 to 25 years a plethora of research worldwide has greatly
increased our understanding of the relationship between exercise, the immune sys-
tem and host protection. My friend, Michael Gleeson, and his students and co-work-
ers have made an important contribution to exercise immunology in capturing and
describing in detail these findings. Michael should be proud of the quality gradu-
ate students he has produced, and their excellent grasp of the complex field of exer-
cise immunology. This book covers the entire spectrum of studies on exercise,
immunology and infection in an organized and readable style. Several other books
on exercise immunology have been published, but none has been targeted to the
Foreword xi
student as has this text. Hopefully this book will be adopted by exercise science and
physiology degree programmes worldwide to further enhance knowledge and inter-
est in exercise immunology.
David C Nieman
References
Hoffman-Goetz L, Keir R, Thorne R et al 1986 Chronic exercise stress in mice
depresses splenic T lymphocyte mitogenesis in vitro. Clinical and Experimental
Immunology 66(3):551-557
Mackinnon LT 1986 Changes in some cellular immune parameters following exercise
training. Medicine and Science in Sports and Exercise 18(5):596-597
Pedersen BK, Tvede N, Hansen FR et al 1988 Modulation of natural killer cell activity
in peripheral blood by physical exercise. Scandinavian Journal of Immunology
27(6):673-678
Petersen AM, Pedersen BK 2005 The anti-inflammatory effect of exercise. Journal of
Applied Physiology 98(4):1154-1162
Simon HB 1984 The immunology of exercise: a brief review. Journal of the American
Medical Association 252(19):2735-2738
xiii
Preface
Exercise immunology is a relatively new area of research. Before 1970 there were
only a handful of papers describing the effects of exercise on the numbers of circu-
lating white blood cells. Since the mid 1970s there has been an increasing number
of papers published on this subject, as illustrated in the graph below.
The data in the graph were obtained from a literature search in PubMed using
the search words ‘exercise immunology’. To date (12 January 2005), 1460 papers are
identified by this search of which 361 (25%) are review articles and 1242 (85%) are
based on human studies. Interest in this area was prompted by mostly anecdotal
reports by athletes, coaches and team doctors that athletes seemed to suffer from a
high incidence of infections (predominantly colds and flu). A few epidemiological
studies in the 1980s and early 1990s appeared to confirm this higher incidence of
upper respiratory tract infection during heavy training in endurance athletes and
following competitive prolonged exercise events. Since then hundreds of studies
have reported that prolonged exercise results in a temporary depression of immune
cell functions. A rather smaller number of studies indicate that a chronic impair-
ment of immune function can occur during periods of intensified training. Even
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xiv PREFACE
fewer studies suggest that moderate regular exercise is associated with improved
immune function and a reduced incidence of infection compared with a completely
sedentary lifestyle. Thus, exercise is not universally bad for the immune system;
rather it is excessive amounts of exercise (possibly in combination with other stres-
sors, e.g. psychological) that result in immune system depression and increased sus-
ceptibility to infection. In recent years studies have focused on the possible
mechanisms by which exercise improves or impairs immune function. Intervention
studies have investigated the effects of diet and nutritional supplements on immune
responses to exercise. Other studies have looked at exercise in environmental
extremes (heat, cold, altitude) and in particular subpopulations (elderly, obese, HIV
patients).
Exercise immunology is now established as an area of research in the discipline
of exercise physiology and is therefore being introduced as an area of study in sport
and exercise science degree programmes in many countries. At present this proba-
bly takes the form of a few lectures within a module devoted to exercise physiol-
ogy, physiology of training, health of the athlete, or exercise and health. In some
universities, however, a full module is devoted to the study of this fascinating sub-
ject at undergraduate or master’s level. More institutions would probably introduce
the subject if a suitable undergraduate text were available. This book is intended to
provide such a text. The subject of exercise immunology is still generally ignored in
standard exercise physiology texts and only a couple of books aimed more at
researchers and postgraduates have been written on the subject. The last of these
was in 1999 and so is already somewhat out of date.
In this book we examine the evidence for the relationship between exercise load
and infection risk. This is followed by a description of the components of the human
immune system and how they function to protect the body from invasion by poten-
tially disease-causing microorganisms. This is not to the same depth as in a clinical
immunology text, but it does cover the essential details of the structure and func-
tion of different immune system cells, soluble factors, the immune response to infec-
tion and how the immune system is organized and regulated. The different ways
that immune function can be measured are also explained. Emphasis here is on the
principles of the tests used and their limitations rather than on the minute detail of
the assay methods. Subsequent chapters describe the known effects of acute exer-
cise and heavy training on innate (non-specific) and acquired (specific) immunity,
the effect of exercise in environmental extremes on immune function and the impact
of nutrition on immunity and immune responses to exercise. In recent years it has
been established that the plasma levels of some cytokines – regulatory molecules
produced by immune cells and other tissues – are markedly altered by exercise and
that some of these cytokines have an influence on fuel metabolism. Hence, one chap-
ter is devoted to this. The field of exercise immunology has many parallels with the
area of psychoneuroimmunology and one of the chapters in this book covers the
impact of acute and chronic psychological stress on immune function and suscepti-
bility to infection. Practical guidelines that have been developed to help minimize
risk of immunodepression and infection in athletes are also explained. Finally, the
importance of the relationship between exercise, infection risk and immune function
in special populations (elderly, obese, diabetic and HIV patients) and the potential
clinical applications of exercise immunology are explored.
This book has been written with the needs of both students and course instruc-
tors in mind. The aim of this book is to enable the student to understand and eval-
uate the relationship between exercise, immune function and infection risk. After
reading this book students should be able to:
Preface xv
● Describe the characteristics of the components of the immune system.
● Explain how these components are organized to form an immune response.
● Appreciate the ways in which immune function can be assessed.
● Understand the physiological basis of the relationship between stress, physical
activity, immune function and infection risk.
● Identify the ways in which exercise and nutrition interact with immune function
in athletes and non-athletes.
● Evaluate the strengths and limitations of the evidence linking physical activity,
immune system integrity and health.
● Provide guidelines to athletes on ways of minimizing infection risk.
In order to reinforce learning, each chapter begins with a list of learning objec-
tives and ends with a list of key points, suggestions for further reading and a list
of references. At the end of the book a glossary provides definitions of all key terms
and abbreviations. The book is structured to provide the basis of a module in exer-
cise immunology that could run over one or two semesters. Each chapter is struc-
tured in a logical sequence, as it would be presented in a lecture, and the tables and
figures used are ones that I and the other contributors currently use in our lectures.
This should reduce the time that course instructors have to spend preparing lectures
and tutorials.
The editor and contributors are all active researchers in exercise and/or stress
immunology. One thing they all have in common is that they all studied or worked
in the School of Sport and Exercise Sciences at the University of Birmingham, which
was one of the first Departments to introduce a module in exercise immunology
into the curriculum of its Sport and Exercise Sciences degree programme. Similar
modules now run at Loughborough, Bangor and Portsmouth Universities and thus
the authors are well versed in teaching this subject which is being continually
updated by new research. Many of the contributors are members of the International
Society for Exercise and Immunology and I (the editor) am an associate editor of a
number of journals, including Exercise Immunology Review. I am particularly proud
of this book as the contributors are all people I have taught as undergraduate stu-
dents and/or supervised as research students.
This book is primarily written for students of sport science, exercise science and
human physiology. It is also relevant to students of medicine, biomedical sciences,
physiotherapy and health sciences. The more practical aspects may also be of inter-
est to athletes, coaches and team doctors. I hope that this book inspires instructors
as well as students to delve more deeply into the subject of exercise immunology.
Most of all, I hope that you enjoy reading our book on this fascinating subject.
Michael Gleeson
Loughborough 2005
1
1
Chapter
Exercise and infection risk
Nicolette C Bishop
CHAPTER CONTENTS
Learning objectives 1 Summary 8
Introduction 1 Heavy exercise and risk of URTI 8
The J-shaped model 2 Anecdotal reports 8
Moderate exercise and risk of URTI 2 Epidemiological studies 8
Anecdotal reports 2 Possible mechanisms 10
Epidemiological data 3 Summary 12
Moderate exercise and URTI Key points 12
symptoms 5 References 12
Possible mechanisms 6 Further reading 14
LEARNING OBJECTIVES:
After studying this chapter, you should be able to ...
1. Describe the J-shaped model of upper respiratory tract infection risk and exercise
volume.
2. Evaluate the evidence concerning moderate exercise and upper respiratory tract
infection risk.
3. Evaluate the evidence concerning heavy exercise and upper respiratory tract infec-
tion risk.
INTRODUCTION
Upper respiratory tract infections (URTI) such as coughs and colds, throat infections
and middle ear infections are a leading cause of visits to general practitioners through-
out the world (Graham 1990). Given that the average adult suffers from two to five
colds each year (Heath et al 1992) it is not surprising that the socioeconomic conse-
quences of these illnesses are considerable in terms of days lost from work and costs
of medical consultation, care and over-the-counter remedies. As such, these illnesses
present a real concern to the wellbeing of both athletes and the general population
and therefore an understanding of the relationship between physical activity and
infection risk is of great importance.