Exercise, Immunity, and Susceptibility to Infection

A J-Shaped Relationship?

Roy J. Shephard, MD, PhD, DPE; Pang N. Shek, PhD

Series Editor: Nicholas A. DiNubile, MD

THE PHYSICIAN AND SPORTSMEDICINE - VOL 27 - NO. 6 - JUNE 1999

In Brief: Regular, moderate exercise enhances immune function and attenuates immune disturbances associated with acute exercise (ie, a single bout of vigorous exercise). Epidemiologic data suggest that vigorous exercise may temporarily reduce resistance to viral infection. However, objective data do not clearly show a J-shaped dose-response relationship between exercise and immune function. Nutritional, hygienic, exercise, environmental, and pharmacologic strategies can minimize the risk of infection. Persons who have systemic symptoms should avoid competition and heavy training.

Some exercise physiologists have postulated a J-shaped relationship between physical activity and susceptibility to viral infection (figure 1). According to this hypothesis, regular moderate physical activity enhances immune responses, reducing susceptibility to the common cold (1-3) and certain cancers (4). In contrast, excessive exercise, such as an ultramarathon or a period of very heavy conditioning, suppresses immunity for several hours to a week or longer, creating a brief period of vulnerability when the risk of upper respiratory tract infections (URTIs)—and possibly of cancer—is increased (5). However, other incidental consequences of, or circumstances related to, exercise could explain some of these changes in susceptibility (6).

The body's normal defenses against infection include physical and biologic barriers. A critical look at the evidence regarding the effects of acute and chronic exercise on these barriers suggests some useful lessons for the prevention and treatment of viral infections in athletes.

Effects of Exercise on the Physical Barriers to Infection

Physical barriers. Many viruses and carcinogens are suspended as droplets in inspired air. Susceptibility is thus influenced by patterns of respiratory airflow and by mechanical barriers (the respiratory endothelium and the mucus that it secretes).

Turbulent airflow through the nose precipitates larger suspended particles, but most viruses remain in suspension until they reach the bronchi. Mucus enhances the effectiveness of the physical endothelial barrier. The tracheal ciliae induce a steady flow of mucus and entrapped particles toward the back of the throat, and this movement is supplemented by coughing and sneezing. Particles are then cleared from the throat by swallowing or expectoration.

Exercise effects. During exercise a combination of high respiratory flow rates and a switch from nose to mouth breathing causes progressive cooling and drying of the respiratory mucosa and increased exposure of the bronchi to air contaminants. The cooling and drying slow cilial movement and increase viscosity of the mucus, thus reducing the clearance of microorganisms and toxic particles from the respiratory tract. In addition, these changes may impair mucosal B cell function, thereby reducing local antibody secretion.

Susceptibility to viruses is increased after a marathon run but not after a 20- to 30-km run, which probably has an almost equal impact on physical barriers (7). It thus seems unlikely that impairment of physical defense mechanisms is a major cause of increased susceptibility to URTI in heavy exercisers.

Effects of Exercise on the Biologic Immune Defenses

Biologic mechanisms. The immediate biologic reaction to infection is an acute inflammation. Local increases in blood flow and vascular permeability facilitate the migration of various leukocytes and plasma proteins into the affected region of the body.

Immediate mechanisms that counter viral infections and destroy fully developed neoplastic cells include the actions of natural killer (NK) cells, phagocytes, and the immunoglobulin A (IgA) present in nasal and bronchial mucus. (Cellular components of the immune system are illustrated in figure 2.) The NK cells can lyse virally infected host cells and tumor cells in the absence of major-histocompatibility-complex (MHC) proteins and cytokine messengers, although their action is enhanced by various cytokines (particularly interferon [IFN]-gamma). In contrast, cytotoxic T cells act only if an antigen is presented to them by a macrophage that has attacked the invading microorganism or tumor cell and processed its surface proteins.

The phagocytes ingest viral particles, destroying them with potent enzymes and chemicals. Soluble elements such as complement and acute-phase protein play a supportive role, attracting phagocytes to the infected region and rendering viral particles more vulnerable to lysis. Specific antibodies, such as IgA, also contribute to early protection, by either preventing the virus from penetrating the endothelial cell membrane or by opsonizing the viral particle (a process that facilitates phagocytosis).

The main biologic defense against infections develops more slowly. A complex sequence of events includes macrocytic phagocytosis of the infecting organism or abnormal cell; killing by lysozymes and/or oxidizing agents; processing of the abnormal surface proteins and their presentation to T cells in association with MHC-restricted protein; and the secretion of cytokines such as interleukin (IL)-1 and IFN-alpha. Proliferation of specific cytotoxic lymphocytes peaks about 7 days after initial triggering of the immune response. B cells, antibodies, and complement also act against certain viruses and tumor cells.

Exercise-induced changes. The main basis for any exercise-induced change in susceptibility to URTIs and neoplasms seems to be a modulation of either the nonspecific or specific biologic defense mechanisms. The effects of exercise on these mechanisms offer some support for the J-curve hypothesis, because regular moderate exercise appears to enhance these mechanisms, whereas very heavy exercise or intensive training appears to weaken them. Both cellular and humoral changes may contribute to the transient depression of immune function (table 1).

Table 1. Physical and Biologic Defenses Against Viral Infection and Neoplastic Cells Physical Mechanisms Filtration mechanisms of the nose Expectoration of particles trapped in nasal and bronchial mucus Integrity of endothelial membrane Biologic Mechanisms Cellular NK cells and cytotoxic lymphocytes: Lyse infected or abnormal cells Phagocytes: Ingest foreign cells; present foreign protein to CD4+ cells Humoral Interferons: Enhance NK cell activity; inhibit viral replication; inhibit or destroy tumor cells Tumor necrosis factor: Inhibit or destroy tumor cells Specific antibodies: Prevent membrane penetration by virus; opsonize virus or abnormal cell Complement and acute-phase protein: Attract phagocytes to affected tissue; increase susceptibility of virus and abnormal cells to lysis

NK cells. Acute exercise induces a substantial, immediate intensity-dependent increase in circulating NK cell count, usually with a matching rise of NK cytolytic activity (5). The response can be mimicked by physiologic doses of catecholamines given at rest (norepinephrine for moderate exercise and epinephrine for more intensive activity). This suggests that NK cells are washed into the circulation during exercise mainly because of a catecholamine-induced alteration in the expression of cellular adhesion molecules at the vascular lining. The greater shear forces associated with an increase in cardiac output may also flush NK cells into the peripheral circulation (5). However, this response is limited to the circulation, and there may be little change in either cell count or antiviral activity in the body as a whole.

In theory, the increase in circulating NK cell numbers and cytolytic activity should augment resistance to viral infections and tumor cells. However, the increase usually persists only as long as exercise continues—too brief a time to have any clinical importance. Moreover, if exercise continues for several hours, the NK cell count and cytolytic activity gradually return toward baseline (8).

Immediately following vigorous, but not moderate, exercise, NK cell counts and cytolytic activity usually drop substantially below normal values, but resting function is often restored within a few hours, leaving only a very brief window of opportunity for viruses and neoplastic cells. It is difficult to reconcile a 2- to 3-hour reduction of NK-cell activity with the reported 2- to 6-fold increase in the incidence of URTIs in the weeks following participation in a marathon or ultramarathon run (2).

Occasionally, immune function has remained depressed for much of the period when NK cells play a dominant role in defense mechanisms. In one study, for example, a disturbance of at least 7 days followed a 90- to 120-minute bout of treadmill exercise at 65% of aerobic power (9). If athletes were to develop a similar prolonged depression of NK cell function, a substantial increase in their risk of viral illnesses might be anticipated.

Possible explanations of the suppression of NK cell activity following vigorous exercise have included a lack of IL-2 and an accumulation of prostaglandins (PG) (5,10). The first hypothesis can probably be discounted, since the addition of optimal quantities of IL-2 to isolated NK cells does not restore normal cytolytic activity. Various prostaglandins are released by tissue microtrauma, and these substances could inhibit NK cell cytotoxic activity (11), although attempts to restore normal function by use of indomethacin have not always been successful (12).

The resting NK cell count is increased by repeated bouts of moderate exercise (5). This could explain why immune defenses are sometimes enhanced in habitual exercisers.

Macrophage activity. The activated macrophage is important to early immune defenses as an initial phagocytic agent, an antigen-presenting cell, and an initial source of lymphocyte-stimulating cytokines. Cell counts are increased by exercise, but normal values are restored within several hours of ceasing physical activity. Moderate exercise increases the cytostatic activity of macrophages, apparently because their production of tumor necrosis factor (TNF) is increased, but very heavy exercise reduces macrophage function (13). Moderate training has little effect on macrophage function, but heavy training reduces macrophage response to inflammation (13). Macrophage activity is down-regulated by PGE₂, whether the PG is generated by muscle microtrauma or a tumor.

T cell counts. Any decrease in CD4+ (T-helper) cell count limits the output of cytokines that activate NK and T cells and stimulate the proliferation and maturation of B cells. An appropriate CD4+/CD8+ (T-helper/T-suppressor) cell ratio of 1.5 or greater is thus important to immune defenses. Both heavy exercise and excessive training can cause this ratio to decrease (5). Further information is needed regarding the importance of maintaining the absolute CD4+ count relative to that of maintaining a CD4+/CD8+ ratio of 1.5 or more. It also remains unclear to what extent an increase in CD4+ count or CD4+/CD8+ ratio, and thus a greater activation of NK cells, can compensate for a decrease in absolute NK cell numbers (and vice-versa).

Proliferative response. Lymphocyte proliferation, stimulated by CD4+ cell-released IL-2, offers the main long-term defense against both viral infections and neoplastic cells. Heavy physical activity or rigorous training reduces this proliferative response (5). This reduction sometimes persists for several hours, contributing to the window of opportunity for viruses and neoplastic cells. On the other hand, moderate training reduces the depression of proliferation induced by any single bout of heavy exercise (14).

Impaired neutrophil function. Secondary bacterial infections can complicate and prolong URTIs. Circulating neutrophil counts often increase dramatically during and for some hours following exercise, but this does not necessarily increase resistance to secondary infection, since phagocytic activity may simultaneously decrease (5,15). Intensive training may decrease the oxidative burst associated with bacterial killing in isolated neutrophils, but, again, the athlete's susceptibility to respiratory infections is not necessarily affected (16).

Cytokines. Exercise increases production of the cytokine IL-1, and resting levels of this substance may also be augmented by training (5). IL-1 has a direct cytotoxic effect. It also stimulates the T cells to produce increased amounts of IL-1 and IL-2, augmenting the cytotoxicity of NK and lymphokine-activated killer (LAK) cells.

IL-2 has an indirect effect on immune defenses, stimulating the function of NK, LAK, and T cells. In vitro studies suggest that exercise decreases free levels of IL-2, possibly by increasing the proportion of lymphocytes that express IL-2 receptors (5).

Interferons slow viral replication. They also alter the surface properties of NK cells and macrophages, with resultant increases in lytic activity (17). Moderate training may increase IFN production, but the output of IFN-alpha is unchanged by several weeks of exhaustive training (5).

TNF-alpha is produced by monocytes. It is cytotoxic, stimulating the activity of macrophages and T and B cells. It also contributes significantly to muscle-wasting in cancer. TNF-ß is produced by active T cells. It is both cytostatic and cytotoxic against tumor cells. Acute exercise increases TNF output, but the effect of training is as yet unknown.

Immunoglobulins. Moderate exercise does not change the concentration of salivary IgA or serum IgG. In contrast, very vigorous exercise decreases IgA concentrations in both saliva and nasal washings. One report found low concentrations for 18 hours following a 31-km race (5). Moderate training increases salivary IgA, but concentrations fall progressively with rigorous training. Partial recovery is seen during precompetitive tapering. Top competitors also show minor decreases in serum IgG concentrations during peak training (18).

Decreases in mucosal IgA concentrations could have an important influence on immune defenses, since secretory IgA inhibits attachment of the virus to the respiratory epithelium, penetration of epithelial cells, and subsequent intracellular replication. Several studies have commented on the coincidence of decreases in salivary IgA and an increased prevalence of URTIs (18).

Other humoral factors. Many other aspects of immunity are influenced by the acute response to exercise. Acute exercise induces increased concentrations of the main acute-phase protein, C-reactive protein; however, the tissue injury associated with heavy training may lead to decreases in resting levels of both serum complement and C-reactive protein (5).

Overall immune responsiveness. The response to vaccines provides one measure of overall immune responsiveness. In the first few days after participation in an Ironman triathlon, there was a reduced response to tetanus and diphtheria toxoid, as well as to purified pneumococcus polysaccharide (19).

Exercise and Susceptibility to Infection

There have been some experimental attempts to examine the influence of acute and chronic physical activity on susceptibility to infection in animals and humans, but most of the evidence is epidemiologic.

Experimental data. Animal observations suggest that excessive and/or stressful exercise weakens host resistance and increases the virulence of certain viruses; mortality rises (20), and the time to death is shortened (21). Human experimental studies have evaluated only moderate exercise, which has little effect on either the likelihood of developing infection or its duration and severity after nasal installation of respiratory viruses (22-24).

Epidemiologic data. Exercise immunologists have often based the diagnosis of respiratory illness on responses to questionnaires rather than clinical examination. Consequently, epidemiologic data may not always provide a valid measure of susceptibility to URTI (see "Limitations of Epidemiologic Research on Exercise and Immune Function," below). However, some findings suggest a dose-response relationship between the volume of physical activity and the likelihood of respiratory symptoms.

Moderate exercise. Moderate exercise has little influence on the risk of URTI in young adults (25,26). Nieman et al (27) noted that 45 minutes of exercise five times per week at 60% of the heart rate reserve reduced the duration of respiratory symptoms but did not affect the incidence of URTI in 25- to 45-year-old women. Any benefit of regular physical activity is more obvious in seniors (28,29), perhaps because they begin an investigation with poor immune function and a low level of physical activity. Among 67- to 85-year-old women, the incidence of URTIs was lowest in a highly conditioned subgroup, intermediate in a subgroup of regular walkers, and highest in calisthenic and sedentary control subgroups (29).

Heavy exercise. There is now a strong consensus that very heavy exercise and/or training increases the prevalence and/or the persistence of respiratory symptoms (table 2). It is less certain that such changes should be attributed to impaired immunity, since few investigators have obtained clinical confirmation of infection or looked for depressed immune function (30).

Table 2. Epidemiologic Studies of Effects of Exercise on Susceptibility to Upper Respiratory Tract Infections (URTIs) in Various Populations
Author	Population	Activity Type and Intensity	Effects on URTI
Douglas and Hanssen (31), 1978	61 rowers, 126 cadets	University rowing (I)	Increased frequency and severity of URTI in rowers
Heath et al (36), 1991	447 m, 83 f, 13-75 yr	Distance running (N)	URTI incidence increased when training distance over 15 km/wk
Karper and Boschen (28), 1993	6 m, 10 f, 60-72 yr	Moderate exercise 3 days/wk (M)	Reduced number of infections relative to initial state
Lee et al,* 1992	96 Air Force cadets	Initial military training (N)	Immune function depressed but no change in URTI incidence
Linde (32), 1987	55 m, 28 f, 19-34 yr	Orienteering (I)	Incidence and duration of URTI greater in orienteers vs controls
Linenger et al (39), 1993	482 m	Special warfare training (N)	High incidence of URTI
Nieman et al (27), 1990	36 f, 25-45 yr	Running 45 min at 60% heart rate reserve 5 days/wk (M)	Reduced duration of URTI symptoms
Nieman et al (7), 1990	2,311 m and f, 35-37 yr	Marathon running (I)	2-fold URTI increase with training; 6-fold increase in faster runners after race
Nieman et al (29), 1993	44 f, elderly	Walking 37 min 5 days/wk (M)	Reduced incidence of URTI relative to controls
Osterback and Qvarnberg (25), 1987	76 m, 61 f, 11-14 yr	Various sports (M, as reported in interview)	No difference between athletes and nonathletes
Peters and Bateman (34), 1983	145 m, 5 f, 18-65 yr	Ultramarathon running (I)	URTI symptoms increased in faster runners
Schouten et al (26), 1988	92 m, 107 f, 20-23 yr	Various, as reported on questionnaire about activity level and fitness (M)	No effect in males; fewer symptoms of URTI in active females
Seyfried et al (33), 1985	8,000 m and f, all ages	Recreational swimming (M)	Increased URTI relative to nonswimmers
Shephard et al (37), 1995	551 m, 199 f, 40-81 yr	Running (N)	16% of subjects had increased URTI incidence if training distance was over 70-80 km/wk
Strauss et al (42), 1988	87 m	Varsity wrestlers, swimmers, gymnasts (I)	86% of subjects reported URTI over 8 wks
Verde et al**1992	10 m	Running, with 38% increase in training volume over 3 wks (N)	Respiratory symptoms in 3 subjects
Weidner et al (24), 1998	34 m and f, 18-29 yr	Various activities, 40 min at 70% heart rate reserve 3 days/wk (M)	No change in duration or severity of URTI in subjects inoculated with rhinovirus
m = male; f = female; M = moderate exercise; I = intense exercise; N = intensity not specified *Lee DJ, Meehan RT, Robinson C, et al: Immune responsiveness and the risk of illness in US Air Force Academy cadets during basic cadet training. Aviat Space Environ Med 1992;63(6):517-523 **Verde T, Thomas S, Moore RW, et al: Immune responses and increased training of the athlete. J Appl Physiol 1992;73:1494-1499

Subjects have included rowers (31), orienteers (32), and swimmers (33), but several of the more detailed studies have involved distance runners. Peters and Bateman (34) noted that in the 2 weeks following an ultramarathon, 33% of runners reported respiratory symptoms, compared with 15% of controls. The prevalence of complaints in those who completed the 56-km event in less than 4 hours increased with running speed and was as high as three times the rate for control nonparticipants. Competitors in a 42-km marathon run were five times as likely to report a URTI as equally trained runners who had not participated in the event (35). On the other hand, 5- to 21-km "fun runs" had no impact on URTI incidence in the participants.

In another study, factors that increased runners' risk of respiratory infection over a 12-month period included running more than 15 km per week, living alone, and having a low body mass index (36). Runners who ran more than 97 km per week were twice as likely to develop URTIs as those who ran less than 32 km per week, even after adjustment for confounding variables (7). In a survey, about 76% of masters athletes considered themselves less vulnerable to colds than their sedentary colleagues, and only 1.5% thought they were more vulnerable (37). Nevertheless, 16% of these athletes thought they became more susceptible when their training reached 70 to 80 km per week.

Among Australian elite athletes, the periods of heaviest training are associated with reduced salivary IgA concentrations and an increased susceptibility to URTIs (38). The incidence of respiratory infections (39) is also increased by heavy military training. However, some elite athletes—cross-country skiers, gymnasts, oarsmen, swimmers, and wrestlers—develop URTIs no more frequently than sedentary people (40-42). Presumably, susceptibility depends on the type and volume of training.

Thus the epidemiologic data provide some suggestion of a dose-response relationship, in that moderate physical activity is associated with an optimal immune response to viral infections and heavy exercise with an impaired immune response. However, current evidence is not yet sufficient to demonstrate a clear J-shaped relationship between the exercise volume and immune function. A similar pattern has been inferred for susceptibility to neoplasms, but here the data are even more limited.

Other Factors Influencing Athletes' Susceptibility to Infection

Pathogen exposure. For athletes, the locale of competition and any requisite air travel may cause exposure to a greater range of infected persons and unfamiliar microorganisms. This alone can increase the incidence of viral infection, even if inherent susceptibility remains unchanged.

Nutrition. Clinical malnutrition is a well-recognized cause of impaired immune function. Most athletes show only small deficiencies of essential nutrients. Nevertheless, they may lack the glutamine needed for lymphocyte proliferation (43,44). Deficiencies in arginine, L-carnitine, essential fatty acids, vitamin B₆, folic acid, vitamin E, and trace elements may also contribute to reduced immune function in athletes (45).

Muscle microtrauma. Cumulative microtrauma from exercise causes local and systemic acute-phase reactions. In the short term, the resulting release of C-reactive protein stimulates monocyte phagocytosis. However, the migration of leukocytes to injured muscle may reduce immune function in other parts of the body, and the generation of oxidant free radicals during the repair process may suppress immune function in a manner analogous to clinical sepsis (46). Perhaps for this reason, antioxidants such as vitamin C reduce the risk of exercise-induced infections (3,47,48).

Environmental influences. Because greater physical activity is associated with a higher socioeconomic status and such status is associated with less exposure to environmental stressors, moderately active people may have less exposure to stressors than sedentary persons have. However, an international competitor encounters many environmental stressors during training and competition. Extremes of heat and cold, high and low ambient pressures, inhalation of polluted air and a resultant acute-phase response in the alveolar macrophages, sleep deprivation, time-zone shifts, and exposure to high and low gravitational forces can all influence immune function adversely (49). Environmental stress can also affect immune function through neurohormonal responses, such as the catecholamines secreted in response to severe cold exposure or the cortisol, IL-1, and IL-6 secretion associated with a rise in core temperature. Finally, an individual in an unfamiliar environment may experience psychological stress and resulting effects on immune function.

Psychological influences. Links between the hypothalamus and the immune system allow psychological factors to modulate the impact of acute and chronic physical activity on immune function (5). The effects of psychological stress and vigorous physical activity tend to be additive, since heavy exercise induces many of the same neurohormonal responses, including substantial secretions of epinephrine, norepinephrine, cortisol, and growth hormone. Athletes plainly face more severe psychological challenges than laboratory subjects who exercise at a similar relative intensity, so they have a greater potential for immune disturbances. For example, as much as a quarter of the variance in virus shedding among individuals inoculated with a rhinovirus can be traced to restricted social contacts and spending too much time in goal-directed activities (50); such a lifestyle has become almost inevitable for athletes who are preparing for international competition.

Implications for Prevention and Treatment

Since heavy physical activity can increase the risk of URTI, and possibly of neoplasia, some practical preventive measures are appropriate, particularly for competitive athletes.

Minimize exposure. Immunosuppression can sometimes reactivate a latent Epstein-Barr virus, but infection generally involves exposure to an external pathogen. Where possible, athletes should thus avoid close contact with individuals who show symptoms or signs of a URTI. Careful hand-washing before meals is important, since hand contact is an important route for transmitting respiratory viruses. The mucosae of the nose and eyes are other potential routes of infection; neither should be rubbed with unwashed hands.

Monitor training. Since immunosuppression commonly seems linked to overtraining, athletes' training intensity should be geared to their physical and nutritional status. The results of most immunologic tests are too variable to provide a useful index of excessive training. However, declining physical performance, excessive fatigue, muscle soreness, depression, and adverse responses to simple psychological tests of mood state such as the Profile of Mood States are warnings that conditioning schedules should be reduced (51).

Control diet. Although clinical malnutrition can significantly impair immune function, the impact of smaller changes in nutritional status is more controversial (45). Inadequate energy intake is common among competitors whose performance is judged in part on physical appearance; whether this deficit is sufficient to limit immune function is unclear. Nevertheless, athletes should take in enough food energy, protein containing a good balance of essential amino acids, and sufficient fiber and antioxidants. In particular, vitamin C supplements can significantly reduce the incidence, duration, and severity of URTIs (3,45,47,48).

Reduce stress. Psychological and environmental stress can interact with heavy training. A recent report (52) noted that the incidence of upper respiratory and gastrointestinal infections in elite runners who trained for 4 weeks at moderate altitudes (1,500 to 2,000 m) was increased 50% relative to training at sea level.

Give chemotherapy and immunotherapy. Inoculations against the viruses prevalent at major international competitions should be updated before departure. Athletes who have a low level of serum immunoglobulins should receive immunomodulating preparations, including intramuscular injections of human immunoglobulins, to help reduce the severity of any contracted disease and perhaps the risk of secondary bronchopulmonary infections (5). Frohlich et al (53) reported that monthly injections of immunoglobulin reduced the duration of infections in swimmers by nearly two thirds relative to swimmers who received a placebo. In contrast, Lindberg and Berglund (54) observed no clinical benefit from the administration of nasal IgA to world-class canoeists.

Multitest Merieux (a cocktail of seven common antigens) allows repeated intradermal assessments of immunocompetence over the course of training. The antigens are inoculated intradermally with a standard applicator, and subsequent inspection of the skin allows assessment of the intensity of the local immune response. Salivary or mucosal immunoglobulin concentrations also can be monitored, although the link between low immunoglobulin levels and an increased susceptibility to infection remains tenuous.

Since one possible mechanism of immunosuppression is an accumulation of prostaglandins, immune function may be helped by the prophylactic or therapeutic use of nonsteroidal anti-inflammatory agents such as indomethacin; however, evidence regarding this measure is conflicting (11,12).

Infection and Competition

Athletes occasionally achieve their best performance despite having a URTI (55), though minor infections often cause them to miss training or competition (29), Physical performance generally decreases during an infection (56), but determining whether the decrease stems from reduced motivation or the effects of the disease is difficult (5).

The performance of most athletes rebounds quite rapidly once an acute illness has passed, although patients occasionally develop a postviral fatigue syndrome (57). A simple URTI responds well to moderation of training and the use of a decongestant by day and an antihistamine at night (55). However, if a viral illness is systemic, exercise must be undertaken cautiously, if at all. Heavy training or competition could increase the severity of disease, and viral myocarditis is a recognized, though rare, cause of death from cardiac arrest during exercise. Warning signs of systemic infection include fever, myalgia, fatigue, cough, vomiting, diarrhea, and lymphadenopathy. Those who have such symptoms, especially recreational athletes, should rest until the symptoms have passed.

Conclusion

The benefits of moderate training include an increased number of circulating natural killer cells. In contrast, intense exercise may cause temporary immunosuppression, suggesting there may be a J-shaped relationship between exercise and immune function. However, the resting level of immune function of competitive athletes may also be greater than that of sedentary persons. Those who are preparing for international competition or involved in exhausting events such as marathons or ultramarathons should consider taking measures to minimize exercise-related immunosuppression. Such measures are not likely to be necessary for recreational athletes.

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Limitations of Epidemiologic Research on Exercise and Immune Function

Much of the evidence on the clinical effects of acute and chronic exercise on immune function has come from epidemiologic studies. Since most findings have been based on questionnaire responses rather than clinical examination, the findings are questionable for several reasons.

Symptoms such as sore throat and nasopharynx, nasal catarrh, and cough with minimal fever are nonspecific and can easily be confused with the respiratory irritation, coughing, and bronchospasm caused by exposure to chemically polluted, cold, or dry air (1). Thus, athletes report substantially fewer upper respiratory symptoms following oral and nasal spray administration of an anti-inflammatory agent (fusafungine).

The questionnaire return rate is also rather low in some studies. For instance, it is 47% in a study conducted by Nieman et al (2). In addition, those who develop an infection, or who fear doing so, are more likely to respond than those who don't. Reporting bias depends on the level of competition. Only about a third of college athletes report upper respiratory tract infections (URTIs) to their physician (3). In contrast, top-level athletes have ready access to medical services; they may perceive even a minor illness as a threat to competitive performance and thus are much more likely than less competitive athletes to report and demand medical treatment for URTIs.

The decision to seek medical advice also depends on an individual's perceived state of health. The anxiety associated with international competition or overtraining tends to worsen perceived health. Thus, top athletes are probably more likely to seek a medical consultation around the time of competition, even if the prevalence of organic disease is unchanged.

References

1. Schwellnus M, Kiessig M, Derman W, et al: Fusafungine reduces symptoms of upper respiratory tract infections (URTI) in runners after a 56 km race, abstract. Med Sci Sports Exerc 1997;29(5 suppl):S296
2. Nieman DC, Johanssen LM, Lee JW, et al: Infectious episodes in runners before and after the Los Angeles marathon. J Sports Med Phys Fitness 1990;30(3):316-328
3. Weidner TG: Reporting behaviors and activity levels of intercollegiate athletes with an URI. Med Sci Sports Exerc 1994;26(1):22-26

The studies of Dr Shephard are supported in part by a research grant from the Defence and Civil Institute of Environmental Medicine.

Dr Shephard is a professor emeritus of applied physiology in the Faculty of Physical Education and Health at the University of Toronto and visiting scientist at the Defence and Civil Institute of Environmental Medicine in Toronto. He is a fellow and past president of the American College of Sports Medicine. Dr Shek is head of the section of operational medicine at the Defence and Civil Institute of Environmental Medicine. Dr DiNubile is an orthopedic surgeon in private practice in Havertown, Pennsylvania, the director of Sports Medicine and Wellness at the Crozer-Keystone Healthplex in Springfield, Pennsylvania, and a member of the editorial board of The Physician and Sportsmedicine. Address correspondence to Roy J. Shephard, MD, PhD, DPE, PO Box 521, Brackendale, BC V0N 1H0, Canada; e-mail to royjshep@mountain-inter.net.