Physical Activity and Stress Resistance: Sympathetic Nervous System Adaptations Prevent Stress-Induced Immunosuppression

Monika Fleshner


Exerc Sport Sci Rev. 2005;33(3):120-126. 

In This Article


Regular, Moderate Exercise is Associated With Improved Overall Health

A physically active lifestyle incurs many health benefits. One recently recognized benefit of regular moderate exercise is stress reduction. The current review develops the hypothesis that physical activity may prevent stress-induced suppression of the immune system and suggests an immunophysiological mechanism (sympathetic nervous system constraint) for this effect.

Regular moderate physical activity positively influences many aspects of health. For example, a physically active lifestyle is associated with decreased risks of coronary heart disease and high blood pressure. A physically active lifestyle may also decrease the risk of bacterial or viral illness. We have proposed that the reported reduction in infectious disease associated with habitual physical activity is caused by an indirect health benefit of exercise, that is, stress reduction. Exposure to physical and/or psychological stressors modulates the immune response. Stressor exposure is neither globally immunosuppressive nor immunopotentiating, but rather immunomodulatory. Factors that modulate the impact that the stress response has on the immune function include the following: the duration of stressor exposure; the perceived controllability of the stressor; the measure of the immune response; and the physiological state of the organism (e.g., young vs old, anxious vs calm, healthy vs ill, and physically active vs sedentary). Voluntary physical activity may prevent stress-induced suppression of the immune system, thereby reducing the increased susceptibility and severity of infectious disease caused by stress.

Exercise, Stress, Disease, and Immune Function

There is early evidence to support the stress-modulatory effect of regular moderate exercise. Brown and Siegal[1] assessed teenage girls (364 subjects) for their levels of self-reported exercise schedules, stress levels, and disease incidence. Although there are limitations to the conclusions that can be drawn from this study because of the failings of self-report and disease verification, the primary findings of this study are clear. As expected, girls who were sedentary and under high levels of stress had elevated disease incidence. In contrast, girls who were moderately physically active and under high stress were protected against the stress-induced increases in disease incidence. Thus, the hypothesis that physical activity may improve health by preventing the immunologically deleterious consequences of stress has support in the human literature.

Similar support can be found in the animal literature using immunological measures as an endpoint. Moraska and Fleshner[13] have recently reported a stress-buffering effect of freewheel running on stress-induced suppression in antibody or immunoglobulin generated against keyhole limpet hemocyanin (αKLH Ig). In this study (depicted in part in Fig. 1), adult male rats (10 per group) were allowed to live with running wheels or remain sedentary in their home cages. After 4 wk of voluntary running, rats were immunized with keyhole limpet hemocyanin (KLH) immediately before exposure to a single session of inescapable tail shock stress (100,1.6 mA, 5-s uncontrollable and unpredictable tail shock). The concentration of antibody generated against KLH was measured in blood using enzyme-linked immunosorbent assay. Assessment of αKLH Ig is an excellent in vivo measure of antigen-specific or acquired immunity because the immune cells remain in the organism, the response requires interactions between several cells of the immune system, the Ig response generated is specific to the antigen used for challenge, and αKLH Ig can be quantitatively measured repeatedly across time. In addition, reductions in an organism's ability to generate αKLH Ig response may be clinically meaningful because it has been reported in humans, as well as in animals, to decline with age and psychological stress. Using this measure we reported that exposure to tail shock stress reduced the αKLH Ig response in sedentary, but not in physically active, rats. Freewheel running alone had no effect on the antibody response.

Figure 1.

Adult male Sprague Dawley rats (N =10 per group) were exposed to either 100 5-s, 1.6-mA tail shocks (60-s random intertrial interval; Stress) or remained in their home cages (No Stress). Immediately before stressor exposure, all rats received an intraperitoneal injection of 200 µg of KLH. Tail vein blood samples were collected weekly and anti-KLH IgG2a (optical density measured using enzyme-linked immunosorbent assay) was measured in serum. Sedentary rats were housed with an immobile running wheel, whereas wheel-running rats were housed with a mobile running wheel. Wheel-running rats were allowed to run for 4 wk before exposure to stress and KLH immunization, and allowed to continue to run throughout the study. [Adapted from Moraska, A., and M. Fleshner. Voluntary physical activity prevents stress-induced behavioral depression and anti-KLH antibody suppression. Am. J. Physiol. Regul. Integr. Comp. Physiol. 281:R484-489, 2001. Copyright © 2001 The American Physiological Society. Used with permission.]

The data presented in Figure 1 suggest that regular, moderate, physical activity can prevent the negative consequences of stress on immune function. The potential immunophysiological mechanism(s) for the stress-buffering effect of exercise are currently undergoing investigation and are the topic of this review. The approach my laboratory has taken to investigate these mechanisms is to conduct research using an accepted model of regular, moderate, habitual exercise (voluntary freewheel running) and a well-characterized model of stress-induced immunosuppression (tail shock-induced suppression of αKLH Ig).


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