Effects of exercise on age- and stress- related attenuation of vaccination responses in mice

Exercise, Stress, Vaccine, Immunity

Sun, Yi

关键词: Exercise, Stress, Vaccine, Immunity;   

Others  :  https://www.ideals.illinois.edu/bitstream/handle/2142/101149/SUN-DISSERTATION-2018.pdf?sequence=1&isAllowed=y

美国|英语

来源: The Illinois Digital Environment for Access to Learning and Scholarship

【 摘 要 】

Several published studies suggest that acute eccentric exercise and exercise training can improve vaccination responses in humans. Normal aging and chronic stress can lead to immunosenescence and immunosuppression, respectively, and there may be a role for exercise in augmenting immune responses under these conditions. However, the underlying mechanisms as to how such exercise might promote this effect is unclear. In order to understand the potential eccentric exercise-induced beneficial effect, verification is needed in an animal model. In the first cohort of experiments, we examined the effects of acute eccentric exercise on primary antibody and cell-mediated responses to vaccination in young mice and aged mice. First, we examined the effects of acute eccentric exercise on primary immune responses to ovalbumin (OVA) vaccination in young mice. Young mice were exercised at 17m/min speed at -20% grade for 45 minutes on a treadmill (ECC1) or remained sedentary (SED). Both ECC1 and SED mice were intramuscularly (IM) injected with 100μg of ovalbumin and 200μg of alum adjuvant immediately after exercise. At three weeks post-exercise, all mice were injected with OVA into the dorsal side of ear to determine the delayed-type hypersensitivity (DTH) response as a measure of cell-mediated immunity to the vaccination. Ear thickness was measured immediately before and every 24h after intradermal treatment. In the second experiment, two bouts of downhill treadmill running were performed on consecutive days (ECC2) and all young mice were vaccinated immediately after the second bout of exercise. In the third experiment, young mice were randomly assigned to an eccentric electrically-stimulated group (ECCstim) or a sham group (Sham). Mice were then vaccinated 6 hours post-exercise. In these three experiments, plasma was collected prior to, and at one, two and four weeks post-vaccination. ELISA was performed to analyze anti-OVA IgG. In all three experiments, there was a significant time main effect indicating plasma anti-OVA IgG was significantly increased at one, two and four weeks relative to pre-immunization. However, there were no significant differences between ECC1, ECC2 or ECCstim and respective control groups, demonstrating that acute eccentric exercise does not improve primary antibody responses in young mice. Also, we did not find significant differences between ECC1 and SED in their DTH responses. Then we replicated the study to determine the effects of acute eccentric exercise on the immune responses to OVA vaccination in aged mice. Aged mice (27 months) in the eccentric exercise group (ECCaged) performed the same single bout of treadmill running as mentioned before. Both ECC and SED mice were IM vaccinated immediately after exercise. Plasma was collected prior to, and at one, two and four weeks post-vaccination. ELISA was performed to analyze anti-OVA IgG. In addition, DTH responses were measured at three weeks post-exercise as mentioned before. We found a significant difference between ECC and SED groups in ear DTH at 24h post-injection, indicating that eccentric exercise increased cell-mediated, but not antibody, responses in aged mice. In conclusion, we found acute eccentric exercise enhanced cell-mediated response in aged mice, but not antibody responses in either young or aged mice. It has been shown that chronic restraint stress suppresses immune responses to vaccination. Therefore, in the second cohort of experiments, we investigated the effects of acute eccentric exercise and voluntary wheel exercise training on antibody and cell-mediated immune responses to vaccination in chronically stressed mice. Mice were randomized into four groups: No stress, Stress-ECC, Stress-VWR and Stress-SED. Mice in the three stressed groups received restraint stress for 6hours/day, 5 days/week for three weeks. Body weights were measured daily immediate after stress session. After one week of stress, Stress-ECC mice performed the same single bout of treadmill running as mentioned before. Stress-VWR mice voluntarily ran on a telemetered wheel for the entire period of experiment. All groups of mice were IM vaccinated immediately after the eccentric exercise. Plasma was collected prior to, and at one, two and four weeks post-vaccination. ELISA was performed to analyze anti-OVA IgG and anti-OVA IgM. In addition, all mice received ear injections after three weeks of stress and DTH responses were measured as mentioned before. We found that restraint stress significantly reduced body weight and caused adrenal hypertrophy. We also found there was a trend that both Stress- ECC and Stress-VWR groups elevated anti-OVA IgM and anti-OVA IgG responses compared to Stress-SED group. In conclusion, acute eccentric exercise and voluntary exercise training trends to alleviate the chronic stress- induced reductions in vaccination responses.