The aging immune system is characterized by the progressive decline in the antibody and T cell-mediated responses to antigen. Little is known, however, about the benefits of exercise in aging on the generation of a primary immune response to antigen and the subsequent antibody and memory T cell-mediated response. Most in vivo immune research to date has utilized vaccines or recall antigens to elicit an immune response. Therefore, the purpose of this experiment was to examine the association of aging and physical activity on the primary antibody and T cell response to the novel protein antigen keyhole-limpet hemocyanin (KLH). Forty-six physically active and sedentary, young (20-35 yr) and older (60-79 yr) men were recruited. Subjects were intramuscularly immunized with 100 microg of KLH, and blood samples were collected at days 0, 7, 14, 21, and 28. Samples were measured for anti-KLH IgM, IgG, IgG1, and IgG2 by ELISA. On day 21 after intramuscular KLH administration, subjects received an intradermal injection with 1 microg of KLH of inflammation recorded at 24, 48, 72, 96, and 120 h to assess anti-KLH delayed-type hypersensitivity response. There was a significant reduction in all anti-KLH measures with aging except for anti-KLH IgG2. The physically active older group had significantly higher anti-KLH IgM, IgG, IgG1, and delayed-type hypersensitivity responses, but not IgG2 compared with the sedentary older group. In conclusion, regular physical activity in older men is associated with a more robust immune response to novel antigenic challenge.

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The mechanism(s) for how physically active organisms are resistant to many damaging effects of acute stressor exposure is unknown. Cellular induction of heat-shock proteins (e.g., HSP72) is one successful strategy used by the cell to survive the damaging effects of stress. It is possible, therefore, that the stress-buffering effect of physical activity may be due to an improved HSP72 response to stress. Thus the purpose of the current study was to determine whether prior voluntary freewheel running facilitates the stress-induced induction of HSP72 in central (brain), peripheral, and immune tissues. Adult male Fischer 344 rats were housed with either a mobile running wheel (Active) or a locked, immobile wheel [sedentary (Sed)] for 8 wk before stressor exposure. Rats were exposed to either inescapable tail-shock stress (IS; 100 1.6-mA tail shocks, 5-s duration, 60-s intertrial interval), exhaustive exercise stress (EXS; treadmill running to exhaustion), or no stress (controls). Blood, brain, and peripheral tissues were collected 2 h after stressor termination. The kinetics of HSP72 induction after IS was determined in cultured mesenteric lymph node cells. Activation of the stress response was verified by measuring serum corticosterone (RIA). Tissue and cellular HSP72 content were measured using HSP72 ELISA in cell lysates. Both Active and Sed rats had elevated levels of serum corticosterone after stress. In contrast, Active but not Sed rats exposed to IS and/or EXS had elevated HSP72 in dorsal vagal complex, frontal cortex, hippocampus, pituitary, adrenal, liver, spleen, mesenteric lymph nodes, and heart. In addition, Active rats exposed to IS demonstrated a faster induction of lymphocyte HSP72 compared with Sed rats. Thus Active rats responded to stress with both greater and faster HSP72 responses compared with Sed rats. These results indicate that previous physical activity potentiates HSP72 expression after a wide range of stressors. Facilitated induction of HSP72 may contribute to the increased stress resistance previously reported in physically active organisms.

Based upon a prior cross-sectional study, we hypothesized that an aerobic exercise intervention in sedentary older adults would improve a primary T cell-dependent immune response. Participants were a subset of older subjects from a large, ongoing exercise intervention study who were randomly assigned to either an aerobic exercise (Cardio, n=30, 68.9 ± 0.8 yrs) or flexibility/balance (Flex, n=20, 69.9 ± 1.2 yrs) intervention. The intervention consisted of either 3 aerobic sessions for 30-60 min at 55-70% VO 2 max or two 60 min flexibility/balance sessions weekly for 10 months. Eight months into the intervention, samples were collected before intramuscular administration of KLH (125 µg), followed by sampling at 2, 3, and 6 wks post-KLH. Serum anti-KLH IgM, IgG1, and IgG2 was measured by ELISA. Physiological and psychosocial measures were also assessed pre-and postintervention. While there was no difference in the anti-KLH IgG2 response between groups, Cardio displayed significantly (p ≤ 0.05) higher anti-KLH IgG1 (at wks 2, 3, and 6 post) and IgM responses when compared to Flex. Despite cardiovascular intervention-induced improvement in physical fitness (~11% vs. 1% change in VO 2 peak in Cardio vs. Flex, respectively), we found no relationship between improved fitness and enhanced anti-KLH antibody responses. Optimism, perceived stress, and affect were all associated with enhanced immune response. We have shown for the first time that cardiovascular training in previously sedentary elderly results in significantly higher primary IgG1 and IgM antibody responses, while having no effect on IgG2 production.

The relationship between glucocorticoids (GCs) and memory is complex, in that memory impairments can occur in response to manipulations that either increase or decrease GC levels. We investigated this issue by assessing the relationship between serum corticosterone (the primary rodent GC) and memory in rats trained in the radial arm water maze, a hippocampus-dependent spatial memory task. Each day, rats learned a new location of the hidden escape platform and then 30 min later their memory of the location of the platform was tested. Under control conditions, well-trained rats had excellent spatial memory and moderately elevated corticosterone levels (approximately 26 microg/dl versus a baseline of approximately 2 microg/dl). Their memory was impaired when corticosterone levels were either reduced by metyrapone (a corticosterone synthesis inhibitor) or increased by acute stress (predator exposure), forming an overall U-shaped relationship between corticosterone levels and memory. We then addressed whether there was a causal relationship between elevated corticosterone levels and impaired memory. If elevated corticosterone levels were a sufficient condition to impair memory, then exogenously administered corticosterone, alone, should have impaired performance. However, we found that spatial memory was not impaired in corticosterone-injected rats that were not exposed to the cat. This work demonstrates that an intermediate level of corticosterone correlated with optimal memory, and either a decrease or an increase in corticosterone levels, in conjunction with strong emotionality, impaired spatial memory. These findings indicate that fear-provoking conditions, which are known to engage the amygdala, interact with stress levels of corticosterone to influence hippocampal functioning.

Most previous stress-immune research focused on the immunosuppressive effects of stress on acquired immunity. More recently, it has become clear that acute stressor exposure can potentiate innate, as well as suppress acquired, immunity. For example, acute stress improves recovery from bacterial inflammation, a classic in vivo measure of innate immunity. The previous work was done in sedentary organisms. Physical activity status can modulate the impact of stress on immune function. The following studies tested the hypothesis that the effect of stress on inflammation after subcutaneous challenge with bacteria ( Escherichia coli) is facilitated by physical activity. The results were that sedentary, stressed rats resolved their inflammation 1–2 days faster and have increased circulating neutrophils compared with their nonstressed, sedentary counterparts. In contrast, physically active, stressed rats resolve their inflammation 3–4 days faster and have increased circulating and inflammatory site neutrophils compared with their nonstressed counterparts. Importantly, the beneficial impact of stress on inflammation recovery and neutrophil migration was greater in the physically active, than sedentary, stressed rats. Thus physical activity status facilitates the positive effect of acute stress on innate immunity.

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Both the alterations in the RBC hemoglobin and lipid proteins are positive health changes associated with exercise training. The impact of the alterations in WBC differentials remains unknown but could indicate a reduction in inflammatory load. In conclusion, freewheel running provides sufficient exercise stimulus to produce some, but not all, training associated physiological adaptations.