I am going to wager a guess that anyone who frequents the gym or thinks about visiting the gym knows a thing or two about which exercises target general muscle groups and is aware of the “no pain, no gain” mantra. The fitness industry, especially over the past decade, is continually growing, leading to a wealth of information but also, misinformation. But apart from the fad diets or eccentric exercise equipment, an increase in trained fitness professionals has led to an abundance of information about caloric intake and training programs, just to name a few. For example, multiple studies have revealed that during a set period of time, resistance training is significantly more effective than aerobic training in terms of maintaining healthy glycemic control, blood pressure and lowering cholesterol. However, this does not discount aerobic exercise as a viable fitness option, especially when attempting to shed pounds, but highlights that resistance training should be incorporated as a major component of your workout schedule, particularly when time is a strong limiting factor. Coincident with our craze for a fit physique is the emergence of a new field of research, exercise immunology. Here, I will add yet another layer of information examining how the immune system is modified by different types of exercise.

Illustrated by Charles Tran.
Illustrated by Charles Tran.

Over the past few years, significant progress has been made in studying the effects of exercise on the immune system. However, the direct effects of exercise on immune homeostasis have been confounded by individual variation in stress hormone levels and body fat composition. Although overall cortisol levels are lower in individuals who exercise regularly, circulating cortisol levels rise in the body during exercise in a pattern that is directly proportional to the intensity of exercise. The same trend has been observed for the catecholamines, epinephrine and norepinephrine. Increasing cortisol and catecholamine levels collectively contribute to an increase in heart rate and an increase in blood flow, as well as maintaining sufficient blood glucose levels to sustain intense physical activity. When studying the influence of long-term exercise, which would include physically active individuals, it is also difficult to discern the direct effects of exercise itself from the indirect effects, such as the reduction of visceral adipose tissue. The presence of visceral adipose tissue is known to increase pro-inflammatory environments, which in turn can be modulated by the levels of stress hormones. Thus, a broad perspective of all these events must be taken into consideration when interpreting exercise studies.

During the initial stages of intense exercise, the number of neutrophils, monocytes, macrophages, NK cells, T cells and B cells are elevated in the blood. These increases are likely attributed to the presence of catecholamines or cortisol, which can alter the cellular expression of adhesion molecules, increase shear stress due to increased blood flow, or stimulate the release of cells from certain tissues. Interestingly, cellular increases of NK, B, CD8+ T cells and a subset of CD4+ T cells might correlate to their expression of β2-adrenergic receptors, which respond to catecholamines.

During the initial stages of acute exercise, the functions of innate cells also appear to be altered. Neutrophils exhibit increased phagocytic and oxidative burst capabilities, macrophages have heightened phagocytic ability in addition to an increase in chemotaxis, whereas NK cells exhibit greater cytotoxicity. Some evidence suggests that T cells are also more responsive to antigen during acute exercise.

However, during the recovery period following exercise, the numbers and functionality of innate and adaptive cells in blood circulation appear to be reduced. Long-term studies performed on regularly active participants have revealed a different picture. Although there were no significant differences in the number of neutrophils observed within the blood, regular exercise does seem to have a limiting effect on the oxidative burst functions of these cells. Interestingly, experiments performed on regular exercisers or exercised mice showed that the number of inflammatory monocytes present within the body is lowered, along with a reduction in macrophage infiltration into chronic inflammatory sites. These observations can be directly related to other recent studies, which have identified an increased proportion of pro-inflammatory macrophages, along with increased chronic inflammation, in the visceral adipose tissue of obese individuals, resulting in an increased risk for diabetes, cancer, cardiovascular and neurodegenerative diseases.

In contrast to the pro-inflammatory cytokines present in visceral adipose tissue, exercise seems to promote an anti-inflammatory environment and the cytokines IL-6 and IL-15 are central to this process. Following muscle contraction, the muscle fibre cells stimulate the release of IL-6, which leads to an increase in fat oxidation and glucose uptake in skeletal muscle. IL-6 also induces IL-1Rα and IL-10 expression, as well as other anti-inflammatory cytokines. IL-15 is also released from skeletal muscle following strength training to stimulate muscle formation. Interestingly, experiments involving IL-15 overexpression in mice resulted in a decrease in visceral adipose tissue volume. Although these cytokines are not thought to have direct roles in suppressing pro-inflammatory cytokines such as TNFα or IL-1β, which are not elevated during or following exercise, they contribute in many other ways to create an anti-inflammatory environment.

Many studies have also been performed on endurance athletes, which include marathon and ultramarathon runners. Although general long-term health benefits are observed from sustained physical activity, immune homeostasis and functionality is dampened during periods of prolonged and intense endurance activities. In some cases, these effects have been observed for days after stopping intense training. The occurrence of upper respiratory tract infections are also increased in seasoned endurance runners, which has been correlated to the reduced production of secretory immunoglobulin A within saliva and other mucosal sites, in addition to decreased numbers and functionality of most immune cells. Coincidentally, pro-inflammatory Th17 cells are increased, whereas regulatory T cells are decreased in the peripheral blood following endurance activity sometimes for up to 10 days. Thus, if you are preparing for an upcoming big race, but are feeling a little under the weather, it is best to reschedule that long run (reschedule is the key term, since rule #1 for marathon runners is to never miss a long run).

A lot of groundwork has been laid for determining the influence of exercise on immune homeostasis and function, but the precise mechanisms remain to be identified. Tailoring experiments to account or control for confounding factors will enable more accurate interpretation of results. Additionally, different types of exercise methods or techniques might also contribute to unique effects within the immune system. However, while exercise immunologists continue to delve into the mechanisms of altered immunity in response to exercise, we can at least look at these studies to plan our training schedules more wisely.

References

Walsh, N.P., et al. Immune function and exercise. Exercise Immunology Review. 17: 6-63 (2011).

Walsh, N.P., et al. Maintaining immune health. Exercise Immunology Review. 17: 64-103 (2011).

The Cure for Everything! Untangling the Twisted Messages About Health, Fitness and Happiness by Timothy Caulfied (2012)

Perry, C., et al. Endurance exercise diverts the balance between Th17 cells and regulatory T cells. PLoS One. 8: e747222 (2013).

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Amanda Moore

Mandy is a former Immunology PhD grad and is doing a postdoc at UCSD studying how the genome of T cells is organized to allow for the timely upregulation and downregulation of gene networks. She is an enthusiast for beer, books, and good debates!
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