Exercise and the Immune System: What’s the Latest Research?
Scientists are untangling the immune system’s involvement in exercise.
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The benefits of exercise on human health are well established, but the question of how exactly exercise improves health continues to intrigue fitness fans and researchers alike. Untangling the immune systems' involvement is one aspect amid increasing efforts to understand the molecular processes that underpin exercise.
Exercise immunology is considered a relatively new area of study, but the connection between exercise and immunity was established back in 1902. Physician Ralph Larrabee conducted a study on the blood of Boston marathon runners, discovering that, after exercise, changes in white blood cell differential counts paralleled those seen in certain diseased conditions.
Over recent years, researchers have investigated the cellular inner workings behind exercise’s effect on the immune system. By understanding the processes at play during exercise, researchers hope to be able to understand how exercise might be harnessed to improve immune health.
Exercise mobilizes anti-inflammatory immune cells
Last year, researchers from Harvard Medical School showed that muscle inflammation caused by exercise mobilizes inflammation-countering T regulatory cells (Tregs). The study, published in Science Immunology indicates that Tregs, long known for their role in autoimmune disease management, are also key players in the body’s immune response during exercise.1
The researchers analyzed what happens in cells taken from mice that ran on a treadmill regularly. These cells were compared to those of mice that ran on a treadmill once, and mice that were sedentary. The muscle cells of the mice that ran on treadmills showed classic signs of inflammation and had elevated levels of Tregs. Further analysis showed that Tregs lowered exercise-induced inflammation. None of these changes were observed in the sedentary mice.
“Our research suggests that with exercise, we have a natural way to boost the body’s immune responses to reduce inflammation,” said Diane Mathis, the study's senior investigator and the Morton Grove-Rasmussen Professor of Immunology at the Blavatnik Institute at Harvard Medical School.
“We’ve only looked in the muscle, but it’s possible that exercise is boosting Treg activity elsewhere in the body as well,” said Mathis.
Studies point to the long-term benefits of exercise
Whilst many studies have investigated temporary boosts to the immune system immediately after exercise, research from York University suggests that some changes are long-term. The study, published in the journal, AJP-Cell, suggests that exercise of moderate intensity increases the production of macrophages.2
Exercise altered the way macrophages used oxygen to generate energy and access their DNA. “Much like if you train your muscles through exercise, we showed that exercise of moderate intensity ended up training the precursors of those macrophages in the bone marrow,” said Ali Abdul-Sater, associate professor and York Research Chair at York University.
In the next phase of this research, Abdul-Sater and collaborators hope to determine which workout routines are most beneficial to the immune system by investigating the inflammatory response in human volunteers.
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Subscribe For FREEExercise increases antibody production post-vaccination
Researchers from Iowa State University investigated whether exercise directly after a vaccine could improve immune response in their study published in Brain, Behavior and Immunity.3
The researchers examined the effect of 90-minute exercises on serum antibody response to 3 different vaccines. Results showed that participants who cycled on a stationary bike or took a brisk walk for 90 minutes after vaccination produced more antibodies in the following 4 weeks in comparison to participants who did no immediate exercise post-immunization.
As to the cause of the increase in immune response, the researchers suggest multiple possibilities, including increased blood and lymph flow and the production of a protein involved in generating virus-specific antibodies. They emphasize that more research is needed to confirm or refute these hypotheses.
Benefits to cancer patients
Given the evidence that exercise has a beneficial impact on the immune system, scientists have also investigated the potential implications it may have on improving cancer prognosis. Researchers at the University of Turku conducted 2 studies involving 28 recently diagnosed lymphoma and breast cancer patients. During the study, the patients did 10 minutes of exercise on a bicycle. Blood samples were taken once before the exercise, and twice after the exercise. The results of the studies were published in Frontiers in Psychology and Scientific Reports.4,5
The researchers analyzed the number of several different immune cells before and after the exercise. They found during the exercise, cytotoxic T cells and natural killer cells increased in the bloodstream of lymphoma patients. In breast cancer patients, the exercise also increased the total number of white blood cells, intermediate monocytes and B cells.
Cancer treatments often reduce the number of circulating immune cells, therefore the possibility of being able to counteract this through exercise has beneficial implications. Tiia Koivula, doctoral researcher at the Turku PET Centre, said. “Further research in cancer patients is needed to study whether the immune cells are transported to the tumor after the exercise, where they could destroy cancer cells. This has been shown to happen in preclinical studies, but research in cancer patients is still rather incomplete.”
Beyond immune cells: The role of the vagus nerve in exercise
Researchers have also recently found interest in the role of the vagus nerve during exercise. The vagus nerve forms part of the parasympathetic nervous system (PNS), often nicknamed the “rest and digest” system. It has been extensively studied for its role in the regulation of many biological processes, including the immune response, and researchers have now discovered the nerve also plays a novel function in exercise.
University of Auckland scientists published findings last year that the activity of these “rest and digest” vagus nerves increases during exercise in a study conducted on sheep. The findings, published in Circulation Research, showed that the vagus nerve releases vasoactive intestinal peptide during exercise, helping coronary vessels dilate and allowing more blood to pump to the heart.6
These findings have potential applications in tackling disease, in particular heart failure. Associate Professor Rohit Ramchandra said, “Our follow-up study will try to see whether we can use this important role of cardiac vagal nerves to improve exercise tolerance in heart failure.” These findings also have implications for treating chronic inflammatory conditions that can arise due to decreased vagus nerve activation.
Advancing our understanding of the impact of exercise on the immune system
While previous research focused on the roles of various hormones released during exercise and their effects on different organs, new studies investigating the physiological changes within cells during exercise will continue to evolve our understanding of how physical activity can be harnessed to benefit the immune system. These findings will have various implications from improving immune responses to vaccinations to improving cancer prognosis.
References:
1. Langston PK, Sun Y, Ryback BA, et al. Regulatory T cells shield muscle mitochondria from interferon-γ–mediated damage to promote the beneficial effects of exercise. Sci Immunol. 2023;8(89):eadi5377. doi: 10.1126/sciimmunol.adi5377
2. Murugathasan M, Jafari A, Amandeep A, Hassan SA, Chihata M, Abdul-Sater AA. Moderate exercise induces trained immunity in macrophages. Am J Physiol Cell Physiol. 2023;325(2):C429-C442. doi: 10.1152/ajpcell.00130.2023
3. Hallam J, Jones T, Alley J, Kohut ML. Exercise after influenza or COVID-19 vaccination increases serum antibody without an increase in side effects. Brain Behav Immun. 2022;102:1-10. doi: 10.1016/j.bbi.2022.02.005
4. Koivula T, Lempiäinen S, Rinne P, et al. Acute exercise mobilizes CD8+ cytotoxic T cells and NK cells in lymphoma patients. Front Physiol. 2023;13. doi: 10.3389/fphys.2022.1078512
5. Koivula T, Lempiäinen S, Rinne P, et al. The effect of acute exercise on circulating immune cells in newly diagnosed breast cancer patients. Sci Rep. 2023;13(1):6561. doi: 10.1038/s41598-023-33432-4
6. Shanks J, Pachen M, Chang JWH, George B, Ramchandra R. Cardiac Vagal Nerve Activity Increases During Exercise to Enhance Coronary Blood Flow. Circ Res. 2023;133(7):559-571. doi: 10.1161/CIRCRESAHA.123.323017
