Word count: 3588



Word count: 3588

Infection, the Immune System and Exercise

David C. Nieman

Department of Health and Exercise Science

Appalachian State University

Boone, North Carolina

Much attention has recently been focused on the relationship between physical and psychological stress, immune function, and upper respiratory tract infections (URTI) such as the common cold and the flu. There is a common belief among the general and athletic populations alike that regular exercise training decreases the risk of acquiring a cold or flu, while severe exertion may increase risk. For example, in the 1989 Runner's World survey, 60.7% of 700 subscribers reported that they had caught fewer colds since beginning to run, while only 4.9% claimed they had caught more.

Some athletes feel that while regular training promotes resistance to URTI, the actual competitive event itself increases their risk. There is considerable anecdotal information from coaches and physicians of athletic teams in support of the belief that severe exertion, especially when coupled with mental stress, places athletes at increased risk for URTI. It has been reported that at the 1988 Olympic Games, some of the world's best athletes were unable to compete due to infectious illness. The URTI that afflicted Olympic gold medalist Sebastian Coe, for example, during the UK Olympic trials, so affected his running that he failed to qualify for his nation's Olympic team. In the 1992 Winter and Summer Olympic Games, a sizable number of athletes reported that they were unable to compete or had sub-par performances because of URTI. Steve Spence, one of America's best hopes for an Olympic medal in the marathon, came down with a fever the night before the event, and was unable to perform as expected, finishing a disappointing 12th.

The Centers for Disease Control has estimated that over 425 million colds and flues occur annually in the United States, resulting in $2.5 billion in lost school and work days, and medical costs. The National Center for Health Statistics reports that more than 90 out of 100 Americans suffer a cold or flu every year. Understanding the relationship between exercise and URTI has potential public health implications, and for the athlete, may mean the difference between being able to compete or missing the event due to illness.

The relationship between physical activity and URTI may be modeled in the form of a "J" curve. (Figure 1). This model suggests that while the risk of URTI may decrease below that of a sedentary individual when one engages in moderate exercise training, risk may rise above average during periods of excessive amounts of exercise. The evidence for and against this model will be reviewed in this chapter.

Infection and Heavy Exertion

Several studies have demonstrated that athletes engaging in marathon type events and/or very heavy training are at increased risk of URTI. In 1987, I researched the incidence of URTI in a group of 2,311 marathon runners who varied widely in running ability and training habits. Using a pilot-tested questionnaire, runners self-reported demographic, training, and URTI episode and symptom data for the two-month period (January, February) prior to and the one week period immediately following the race.

An important finding was that 12.9% of Los Angeles Marathon (LAM) participants reported getting sick during the week following the race in comparison to only 2.2% of similarly experienced runners who had applied but did not participate (for reasons other than sickness). After statistically controlling for important demographic and training data, it was determined that the odds were 6 to 1 in favor of sickness for the LAM participants versus the nonparticipating runners. (Figure 2).

Forty percent of the runners reported at least one URTI during the two month winter period prior to the LAM. Controlling for important confounders, it was determined that runners training more than 96 kilometers per week doubled their odds for sickness compared to those training less than 32 kilometers a week. Although the lowest odds of sickness were in the less than 32 km/week group, the odds ratio did not increase significantly until 96 km/week were exceeded. (Figure 3). The researchers concluded that runners may experience increased risk for URTI during heavy training or following a marathon race event.

Other survey data support these findings. In South Africa, the incidence of URTI was studied in 150 randomly selected marathon runners who took part in a 56 kilometer race in comparison to matched controls who did not run. Symptoms of URTI occurred in 33.3% of runners compared with 15.3% of controls during the two week period following the race, and were most common in those who achieved the faster race times. (Figure 4). The most prevalent symptoms after the race were reported to be sore throats and nasal symptoms. Of the total number of symptoms reported by the runners, 80% lasted for longer than three days, suggesting that the runners were infected with a virus. Two other studies conducted in South Africa have shown similar results -- runners are more likely than normal to get sick after marathon or ultramarathon endurance race events.

The Immune System

Our bodies are exposed constantly to an army of bacteria, viruses, fungi, and parasites which seek to invade our bodies, causing infection and sickness. Fortunately, our bodies have a strong "department of defense" composed of white blood cells for combating these infectious agents. There are several major types of white blood cells (see Figure 5), and these cells all work together to fend off invading armies of germs.

There are approximately 7,000 white blood cells per microliter of blood. Nearly two-thirds of these are granulocytes (mainly neutrophils), with 30% of them classified as lymphocytes, and 5% monocytes. Lymphocytes are approximately 75% T cells, 15% natural killer (NK) cells, and 10% B cells.

T cells are further divided into T helper cells (which when stimulated secrete various chemicals that improve immune function), and T cytotoxic/suppressor cells (which after activation will destroy foreign bacteria and viruses).

The immune system is comprised of two functional divisions--the innate, which acts as a first line of defense against foreign agents, and the adaptive, which when activated produces a specific reaction and subsequent immunological memory to each foreign agent. The innate immune system is composed of physical barriers (e.g., the skin and mucosal surfaces), neutrophils, macrophages, NK cells, and certain chemicals. Neutrophils and macrophages can engulf particles, internalize them, and destroy them. Macrophages also act as sentries, secreting chemical messengers that summon other cells such as neutrophils that are better killers.

The adaptive immune system consists of B and T lymphocytes that have the ability to recognize foreign materials, divide and proliferate, and then secrete chemicals or engage in direct killing actions to destroy the foreign agent. They also remember what they have done, and thus are ready to act more rapidly and fiercely in subsequent exposures. Antibodies or immunoglobulins which are secreted from B cells act as flexible adapters which help the neutrophils and macrophages bind foreign materials more easily.

Effect Of Heavy Exertion On The Immune System

Several researchers have reported that immune system

function is suppressed for several hours following intense, prolonged endurance exercise. Heavy exertion is a form of stress that causes large increases in epinephrine and cortisol levels, hormones from the adrenal glands which have been consistently associated with a suppression of immune function, and rapid, large alterations in numbers of white blood cells in the blood.

In a study conducted in my laboratory, 10 seasoned marathoners ran at their fastest marathon pace on treadmills for 3 hours. Cortisol rose 60% above normal after the marathon run, remaining elevated for 1.5 hours of recovery before falling to normal daytime levels. This increase in cortisol was associated with a significant decrease in the function of blood NK cells which persisted for nearly 6 hours. (Figure 6). NK cells usually respond rapidly to foreign materials, and initially control them until other aspects of the immune system begin to respond. The activity of NK cells represents a major first line defense system against viral infection, and can be considered as the "marine corps" of the immune system. This study showed that for at least 6 hours after a marathon, the body's first line of defense is impaired.

The ability of another type of lymphocyte, the T cell, to proliferate (or clone themselves) after coming in contact with foreign material is an important component of the immune response. Two research teams from Finland and the United States studied runners after they ran a marathon, and both reported a significant decrease in T cell proliferative response for

several hours after a marathon. This is yet another indication that the immune system is suppressed after heavy exercise. The temporary impairment of both NK cell activity and T cell proliferation following a marathon may partially explain why athletes are at increased risk for respiratory infection.

Other components of the immune system may be chronically affected by the strenuous training that elite endurance athletes sustain. Neutrophil killing capacity and immunoglobulin concentrations in the saliva have been determined to be chronically suppressed in elite endurance athletes in comparison to untrained individuals. Russian investigators have related that exhaustion of immune reserves can be observed during periods of important competitions, manifested by lowered blood immunoglobulin levels and suppression of neutrophil killing capacity. Results from animal studies have rather consistently supported the viewpoint that both heavy exertion is related to negative changes in immune function.

Psychological factors may also play an important role in the relationship between exercise and URTI. Mental stress has been shown by several researchers to increase one's risk of URTI. In one 6-month study in Australia, highly stressed individuals were measured to have twice as many days with URTI symptoms as compared with low-stressed people. When subjects are given nasal drops containing cold viruses, those who were highly stressed were more likely to get sick than those with little stress. Bereavement, major depression, loneliness, marital discord, and other forms of mental stress have all been

associated with suppression of immune function.

Although specific research in this area has not yet been conducted, it would seem logical to assume that athletes around the time of competition, when both physiological and psychological stress are high, would be most vulnerable to respiratory infections. In such circumstances, the combined psychological and physiological impact may overwhelm the ability of the immune system to protect the host.

Moderate Exercise Training And Infection

What about the common belief that moderate physical activity is beneficial in decreasing risk of URTI and improving immune function? Very few studies have been carried out in this area, and more research is certainly warranted to investigate this interesting question.

In a randomized, controlled study, I measured the effect of walking on the immune response and incidence of URTI in a group of sedentary, mildly obese women. The exercise subjects walked 45 minutes/session, 5 times/week, for 15 continuous weeks on a measured course under supervision. Subjects recorded health problems in a daily log book using 10 codes supplied by the Centers for Disease Control.

Exercise subjects experienced one-half the days with URTI symptoms during the 15-week period compared to that of the sedentary control group (Figure 7). Moderate exercise training led to a 20% net increase in each of the three serum immunoglobulins and a 57% increase in NK cell activity, helping to explain why the women who walked were sick fewer days.

Other studies have shown that active versus sedentary people have higher NK cell activity. In Denmark, people who exercise on bicycles were found to have enhanced NK cell function when compared to sedentary individuals. In a 16-week study of elderly women, moderate exercise was associated with a 33% higher NK cell activity at rest. In another recent study of elderly women, I found that the incidence of the common cold was much lower in a group of elderly women who walked 40 minutes, 5 times a week for 12 weeks during the fall season as compared to a sedentary control group (21% vs 50%, respectively).

Researchers in Australia have shown that one hour of cycling at 60% VO2max may increase resistance to infection by improving the "killing capacity" of neutrophils, an effect which persists for at least 6 hours of recovery. In that neutrophils are the body's best white blood cell for killing foreign agents, these findings suggest that regular episodes of moderate exercise may increase resistance to infection. It appears that beneficial changes in immune function occur during and after each moderate exercise bout suggesting that daily exercise bouts may be important in reducing the risk of colds and flues.

Summary and Practical Implications

As reviewed in this chapter, evidence from many research studies support the concept that heavy exertion increases the athlete's risk of URTI because of negative changes in immune function. On the other hand, there is growing evidence that "moderate" amounts of exercise may actually decrease one's risk of URTI while improving immune function.

Elite athletes do not have the option of training moderately on a regular basis. Instead, most go through various phases of intense training and competition to achieve their personal goals. Nonetheless, several precautions can help athletes reduce their risk of URTI. Considerable evidence indicates that two other environmental factors, improper nutrition and psychological stress, can compound the negative influence that heavy exertion has on the immune system. Based on current understanding, the athlete is urged to eat a well-balanced diet, keep other life stresses to a minimum, avoid overtraining and chronic fatigue, shun sick people before and after important events, obtain adequate sleep, and space vigorous workouts and race events as far apart as possible. If the athlete is competing during the winter months, a flu shot is highly recommended.

If an athlete experiences sudden and unexplained deterioration in performance during training or competition, viral infection should be suspected. It is well established that athletes are unable to perform normally during an infectious episode. If signs and symptoms indicate that a viral infection is impending, the athlete should greatly reduce the volume and intensity of training to allow the immune system to give full attention to combating the illness. Most experts recommend that if the athlete has symptoms of a common cold with no other symptoms (i.e., in the head only), then regular training may be safely resumed a few days after the resolution of symptoms. Mild exercise during sickness with the common cold does not appear to be contraindicated. However, if there are symptoms or signs throughout the whole body such as occurs during the flu (fever, extreme tiredness, muscle aches, swollen lymph glands, etc.), then two weeks should be allowed before resumption of intensive training to avoid relapse and/or potential life-threatening complications such as infection of the heart muscle. There have been several documented cases of individuals dying after intensive exercise conducted during times of respiratory sickness.

For the fitness enthusiast, the area of concern is not so much the harm that may come from overexertion, but the benefits that may derive from engaging in regular, moderate forms of exercise. Most experts now recommend that the immune system is benefited most when individuals engage in moderate exercise (less than 60% maximal capacity) for 30 to 60 minutes several times a week. People who adopt such an exercise lifestyle should over the years experience less days with sickness, and more energy for work and leisure activities. (See SIDEBAR).

References

1. Heath, G.W., C.A. Macera, and D.C. Nieman. Exercise and Upper Respiratory Tract Infection: Is There A Relationship? Sports Med. 14:353-365, 1992.

2. Khansari, D.N., A.J. Murgo, and R.E. Faith. Effects of stress on the immune system. Immunol. Today 11(5):170-175, 1990.

3. Kusaka, Y., H. Kondou, and K. Morimoto. Healthy lifestyles are associated with higher natural killer cell activity. Prev. Med. 21:602-615, 1992.

4. Male, D. and I. Roitt. Adaptive and innate immunity. In Roitt, I.M., et al., eds. Immunology (2nd edition). New York: Gower Medical Publishing, 1989.

5. Nehlsen-Cannarella, S.L., D.C. Nieman, A.J. Balk-Lamberton, et al. The effects of moderate exercise training on immune response. Med. Sci. Sports Exerc. 23:64-70, 1991.

6. Nieman, D.C. Physical Activity, Fitness and Infection. In Bouchard, C., ed. Exercise, Fitness, and Health: A Consensus of Current Knowledge. Champaign, IL: Human Kinetics Books, 1993 (in press).

7. Nieman, D.C., L.S. Berk, M. Simpson-Westerberg, et al. Effects of long endurance running on immune system parameters and lymphocyte function in experienced marathoners. Int. J. Sports Med. 10:317-323, 1989.

8. Nieman, D.C., D.A. Henson, G. Gusewitch, et al: Physical activity and immune function in elderly women. Med. Sci. Sports Exerc. 25:000, 1993.

9. Nieman, D.C., L.M. Johanssen, J.W. Lee, and K. Arabatzis. Infectious episodes in runners before and after the Los Angeles Marathon. J. Sports Med. Phys. Fitness 30:316-328, 1990.

10. Nieman, D.C. and S.L. Nehlsen-Cannarella. Effects of endurance exercise on immune response. In Shephard, R.J. and P.O. Åstrand, eds. Endurance in Sport. Oxford, England: Blackwell Scientific Publications LTD, 1992.

11. Nieman, D.C. and S.L. Nehlsen-Cannarella. Exercise and infection. In Eisinger, M. and R.W. Watson, eds. Exercise and Disease. Boca Raton, FL: CRC Press, Inc., 1992.

12. Nieman, D.C. and S.L. Nehlsen-Cannarella. The effects of acute and chronic exercise on immunoglobulins. Sports Med. 11:183-201, 1991.

13. Pedersen, B.K. Influence of physical activity on the cellular immune system: Mechanisms of action. Int. J. Sports Med. 12(suppl 1):S23-S29, 1991.

14. Peters, E.M. and E.D. Bateman. Respiratory tract infections: an epidemiological survey. S. Afr. Med. J. 64:582-584, 1983.

SIDEBAR

Science has yet to discover a cure for the common cold and flu. Thus prevention from becoming infected is one strategy practiced by some hopeful individuals. While the proper use of nonprescription drugs such as decongestants, antihistamines, and cough suppressants can be effective in relieving many of the symptoms, they do not cure these conditions.

Preventing colds and flues, most scientists agree, is ideally accomplished by avoiding exposure to the viruses that cause them. The viruses are spread by microscopic droplets of body fluid from secretions we breathe out all the time. Our hands, eyes, lungs, and skin are in contact with them constantly. Many researchers believe that as we rub our eyes, touch our mouths and noses, we bring the virus into contact with mucous membranes that transmit the virus into our bodies. As we breathe the air near sick people, the viruses can also be transported in. Completely avoiding cold and flu viruses thus appears nearly hopeless unless we live as a hermit on some distant Pacific island.

Thus having a strong immune system within our bodies becomes all important. If the war cannot be prevented, a strong defense system may win the day. As the viruses enter the body, they encounter a legion of nearly one trillion highly specialized cells that have the marvelous ability to identify and destroy all foreign substances. Keeping this army vigilant and healthy is where you get involved.

The immune system can be weakened or strengthened by several lifestyle factors, including exercise, diet, and mental stress. It is well known that malnourished or highly stressed individuals are more prone to all sorts of infectious diseases including the common cold and the flu because of enfeebled immune systems. To shore up your defenses, eat a well-balanced diet rich in vitamins and minerals from whole grains, fruits, vegetables, and low-fat dairy and meat products. Try to keep life stresses to a minimum, get 7-8 hours of sleep each night, and engage in 30-60 minutes of moderate exercise several times a week.

FIGURE LEGENDS

Figure 1 "J"-shaped model of relationship between varying amounts of exercise and risk of URTI. This model suggests that moderate exercise may lower risk of respiratory infection while excessive amounts may increase the risk.

Figure 2 Upper respiratory tract infections (URTI) in 2,311 Los Angeles marathon runners during the week following the 1987 Los Angeles Marathon. Runners who ran the marathon were 5.9 times more likely than nonparticipating runners to get sick.

Figure 3 Upper respiratory tract infections (URTI) in 2,311 Los Angeles marathon runners during the two-month period (January, February) prior to the 1987 Los Angeles Marathon. Runners training more than 96 kilometers per week doubled their odds of getting sick.

Figure 4 Upper respiratory tract infections (URTI) in runners versus controls during a two week period following a 56 kilometer race in South Africa. About one-third of the runners got sick compared to 15% of non-runner controls.

Figure 5 Cells of the human immune system (see text for explanation).

Figure 6 Changes in NK cell activity in 10 male marathon runners in response to a 3-hour run on the treadmill at 70% VO2max. NK cell activity was depressed for at least six hours after this hard bout of exercise.

Figure 7 Moderate exercise training effects on the total number of upper respiratory tract infection symptom days during a 15-week period in 18 walkers versus 18 sedentary controls. Notice that women in the walking group had half the days with symptoms of sickness compared to the sedentary control group.

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