Adam Persky, Andrew Doyle, Chris Martens, Dennis Ryan
The medical world has made great advances in treatments relating from high blood pressure to HIV and cancer. One of the most common recommendations in most types of follow up treatments is to maintain a high quality diet and participate in an excise program on a regular basis. These suggestions are made because exercise has been proven to decrease LDL cholesterol levels while increasing HDL levels. In addition, exercise is known to decrease blood pressure and provoke a general overall feeling of contentment and well being. As we well know there is much to be said about the perception we have of our selves as it relates to our interaction with others. Unfortunately, some individuals insist on taking things to extremes and in these situations too much of a good thing can be detrimental to a person's health. Highly trained endurance athletes are frequently ill either from colds or flu or more serious forms of upper respiratory tract infections (7). Case in point, Irvin "Magic" Johnson, one of the all time great basketball players is HIV positive but still manages to maintain a extremely high level of activity. Has he in fact increased his life expectancy because of his commitment to a healthy lifestyle which includes an intense exercise regimen? The question that needs to be answered is in relation to our immune system; how much is too much and is there an ideal prescription for the levels of exercise the general public should be getting to achieve the maximal potential of the immune system.
How does exercise affect leukocyte populations and/or activity?
When dealing with endurance exercise there are generally three levels of exercise intensity: low, moderate, and high. These levels correspond to an oxygen consumption rate (VO2) and/or level of sustained heart rate during exercise. Most health benefits from exercise comes from moderate (<1 hr, 3-5 days/wk ( <65% VO2max) to high intensity (>1 hr, 5-7 days/wk >65% VO2max) exercise.
How does moderate and high intensity bouts effects neutrophils (PMN)?
Neutrophil counts are higher in athletes but the activity of the
neutrophils are diminished (10). Acute bouts of exercise induces an
increase in PMN numbers. This has been directly correlated with the
intensity and duration of the exercise bout. Cycling at 60% VO2max for
one hour results in PMN's being primed for their respiratory burst for
up to 6 hours post-exercise (10). Moderate exercise also causes a
increase in high activity cells which possibly increases PMNs phagocytic
and killing abilities (10).
High intensity training depresses some neutrophil functions chronically with possible increases in their killing ability. This level of exercise results in a primed PMN chemotactic response to super oxides and will lead to a 2 fold increase in PMN phagocytic capacity (10). In addition, intense training decreases the adhesive capacity by 3 fold; however, this information is questionable. The decrease observed may result in a decreased ability of PMN's to extravasate into tissue at the sight of infection, leading to a possible decreased ability to rid the body of the infection. The significance of these occurrences is still unknown (10).
What does moderate and high intensity bouts affect natural killer cells (NK)?
When comparing athletes to non-athletes, regardless of age, the natural killer cell activity is enhanced in the athletic population. Evidence suggests that moderate intensity exercise increases the numbers of NK cells and the number of circulating lymphocytes (2,5). NK activity peaks immediately following exercise and drops to subnormal levels over the next 120 minutes. This activity level gradually recovers over the next 20 hours. The long-term response of NK cells to exhaustive exercise is less favorable because there is a possible down-regulation of NK activity. Evidence that low intensity exercise increase the numbers of NK cells and the number of circulating lymphocytes(2, 5).
Heavy training induces a prolonged depression of the NK/ IL-2 system, and this change is probably responsible for the vulnerability to acute infection associated with both single bouts of very strenuous physical activity and chronic over-training (8). It has been clearly shown in several studies that the incidence of highly trained athletes contracting a upper respiratory infection (URTI) is increased following marathons and other long endurance events where athletes are performing for long time periods at a high percentage of their VO2max (7). As little as 90-120 minutes of exercise at 60% VO2 max can lower peripheral blood NK activity for a week or more (8). NK cytolytic activity has been found to be poor in AIDS patients, and in such individuals cytolysis could be augmented by infusion of IL-2 because IL-2 could be the immediate signal to induce the production of cytotoxic factors by the NK cells (8).
What does moderate and high intensity bouts affect lymphocyte populations activity level?
Overall, the innate immune response responds to intense exercise but the adaptive immune response is largely unaffected. When considering just the older population, T cell function is enhanced in elderly trained individuals when compared to untrained individuals of the same age (4). One study examined a 15 week exercise training protocols effect on the immune cells of subjects. The exercise group had significant decreases in lymphocyte percentage, however no effect was observed on the total leukocyte count, spontaneous blastogenesis, T helper/inducer cell number, T cytotoxic/suppressor cell number or helper/suppressor T cell ratio (4). In other studies, T-cell response has been reported to decrease for up to 3 hours after a marathon but not shorter distance running. This will also vary with fitness level. It is unknown whether or not this will influence susceptibility to infection (2).
What is the clinical implication of these leukocyte changes?
Can exercise benefit those afflicted with HIV/AIDS or cancer?
Since studies led to some clarification of how immune cells are affected
by exercise, it is important to apply this information to clinical
situations. Evidence suggests that 45 minutes to an hour of aerobic
exercise at 70-85 % of their maximum heart rate causes an increase in
the number of CD4 cells in individuals with HIV/AIDS (1,6). This
increase only results in normalization of CD4 levels not to supra-normal
levels. These increases in CD4 cells are most significant in less
immuno-compromised individuals. Additionally, endurance training
increases size and number of mitochondria which may counteract the
affects of zidovudine (AZT) which has been shown to cause mitochondrial
myopathy (3). Finally the increase in levels of endorphins,
enkephalins, and natural opiods as a result of exercise can help to
reduce psychological stress which has been shown to compromise the
immune system and may enhance the well-being of those afflicted with the
HIV virus (1).
Much data for the association of exercise and cancer are from epidemiological studies. Because of this fact it is difficult to demonstrate an association between exercise and cancer because of many confounding factors (9). Moderate exercise has been shown to reduce certain types of cancers especially colon tumors and tumors/cancer of the female reproductive tract (9). Those who exercise generally have a healthy lifestyle and diet which may prevent many diseases in and of itself. Exercise does deplete glycogen stores and plasma amino acids which could limit the energy supply of immunological cells (9). In addition, exercise also increases the rate of free radical production which can increase genetic change and tumor production. Fortunately, exercise increases the activity of antioxidant enzymes and augments ascorbic acid and tocopherols reserve (9).
Research in the area of exercise immunology is a relatively new endeavor. Ethical constraints preclude direct human experiments to examine the possible value of regular exercise in the treatment of experimentally-induced HIV and cancer in humans (9). Using exercise to help in the treatment of HIV or cancer patients is also difficult because one cannot ask these population to stop their pharmacological treatment so investigators can study the affect of exercise alone. The use of animals to study exercise's effects are also questionable because does animal models provide a normal, free-living human model (9). This area of research has just started to elucidate the effects of exercise on immune function and this research may prove invaluable in the treatment of disease.