Recovery of the immune system after exercise.

TLDR: The notion that prolonged, intense exercise causes an "open window" of immunodepression during recovery after exercise is well accepted as discussed by the authors, and it has been shown that repeated exercise bouts or intensified training without suff...

Abstract: The notion that prolonged, intense exercise causes an “open window” of immunodepression during recovery after exercise is well accepted. Repeated exercise bouts or intensified training without suff...

Figures

Table 1. Evidence heatmap comparing differences in immune responses to two versus one exercise bout on the same day (A), short vs long recovery between bouts on the same day (B), consecutive days of exercise (C), and weeks (D) or months (E) of intensified training.

Figure 2. Summary of the effects of nonsteroidal anti-inflammatory drugs (NSAIDs) and 829 physical therapies on immune changes during recovery from exercise. 830

Figure 1. Overreaching or heavy training is associated with impaired cellular immune function 809 and latent viral reactivation. Reduction in lymphocyte trafficking and function during exercise 810 recovery impairs immune surveillance, which may increase susceptibility to opportunistic 811 infection. Lowered immunity may also allow previously acquired viruses to reactivate from a 812 latent state, which may cause further immunodepression and increase susceptibility to 813 infection. 814

Full text

PRIFYSGOL BANGOR / B
ANGOR UNIVERSITY
Recovery of the immune system after exercise
Peake, Jonathan M; Neubauer, Oliver; Walsh, Neil P; Simpson, Richard J
Journal of Applied Physiology
DOI:
10.1152/japplphysiol.00622.2016
Published: 01/05/2017
Peer reviewed version
Cyswllt i'r cyhoeddiad / Link to publication
Dyfyniad o'r fersiwn a gyhoeddwyd / Citation for published version (APA):
Peake, J. M., Neubauer, O., Walsh, N. P., & Simpson, R. J. (2017). Recovery of the immune
system after exercise. Journal of Applied Physiology, 122(5), 1077-1087.
https://doi.org/10.1152/japplphysiol.00622.2016
Hawliau Cyffredinol / General rights
Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or
other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal
requirements associated with these rights.
• Users may download and print one copy of any publication from the public portal for the purpose of private
study or research.
• You may not further distribute the material or use it for any profit-making activity or commercial gain
• You may freely distribute the URL identifying the publication in the public portal ?
Take down policy
If you believe that this document breaches copyright please contact us providing details, and we will remove access to
the work immediately and investigate your claim.
10. Aug. 2022

1
Recovery of the immune system after exercise
Jonathan M. Peake
1,2
, Oliver Neubauer
1
, Neil P. Walsh
3
, Richard J. Simpson
4
1
School of Biomedical Sciences and Institute of Health and Biomedical Innovation,
Queensland University of Technology, Brisbane, Australia.
2
Centre of Excellence for Applied Sport Science Research, Queensland Academy of
Sport, Brisbane, Australia.
3
Extremes Research Group, School of Sport, Health and Exercise Sciences, Bangor
University, Bangor, UK.
4
Laboratory of Integrated Physiology, Department of Health and Human Performance,
University of Houston, Houston, Texas, USA.
Running head: Immune system recovery after exercise
Word count in main document: 5,253
Corresponding author:
Jonathan Peake
Institute of Health and Biomedical Innovation
Queensland University of Technology
Kelvin Grove, QLD 4059
Australia
Email: jonathan.peake@qut.edu.au
Phone: +61 7 3138 6140

2
ABSTRACT 1
The notion that prolonged, intense exercise causes an ‘open window’ of 2
immunodepression during recovery after exercise is well accepted. Repeated exercise bouts 3
or intensified training without sufficient recovery may increase the risk of illness. However, 4
except for salivary IgA, clear and consistent markers of this immunodepression remain 5
elusive. Exercise increases circulating neutrophil and monocyte counts, and reduces 6
circulating lymphocyte count during recovery. This lymphopenia results from preferential 7
egress of lymphocyte subtypes with potent effector functions (e.g., NK cells,  T cells and 8
CD8
+
T cells). These lymphocytes most likely translocate to peripheral sites of potential 9
antigen encounter (e.g., lungs, gut). This redeployment of effector lymphocytes is an integral 10
part of the physiological stress response to exercise. Current knowledge about changes in 11
immune function during recovery from exercise is derived from assessment at the cell 12
population level of isolated cells ex vivo or in blood. This assessment can be biased by large 13
changes in the distribution of immune cells between blood and peripheral tissues during and 14
after exercise. Some evidence suggests that reduced immune cell function in vitro may 15
coincide with changes in vivo and rates of illness after exercise, but more work is required to 16
substantiate this notion. Among the various nutritional strategies and physical therapies that 17
athletes use to recover from exercise, carbohydrate supplementation is the most effective for 18
minimizing immune disturbances during exercise recovery. Sleep is an important aspect of 19
recovery, but more research is needed to determine how sleep disruption influences the 20
immune system of athletes. 21
22
Keywords: open window; repeated exercise bouts; immunodepression; overreaching; sleep23

3
INTRODUCTION 24
The immune system is integral to the body’s defense against infection. It also influences 25
other physiological systems and processes, including tissue repair, metabolism, 26
thermoregulation, sleep/fatigue, and mental health. Over the past 40 years, exercise 27
immunology has developed into its own discipline based on the recognition that the immune 28
system mediates many exercise effects and that stress responses mediated through the 29
nervous and endocrine systems play a key role in determining exercise-induced immune 30
changes (84). A classic paradigm in exercise immunology is that an ‘open window’ of 31
immunodepression can occur during recovery from intense exercise. In particular, this 32
paradigm proposes that after intense exercise, some immune variables (e.g., lymphocyte and 33
natural killer cell numbers, antibody production) transiently decrease below preexercise 34
levels. As a result of this immunodepression microbial agents, especially viruses, may invade 35
the host or reactivate from a latent state, leading to infection and illness (87). If exercise is 36
repeated again while the immune system is still depressed, this could lead to a greater degree 37
of immunodepression and potentially a longer window of opportunity for infection (87). 38
Exercise-induced fatigue exists on a continuum. Repeated bouts of intense exercise on the 39
same day or over several days may cause acute fatigue, as indicated by an inability to maintain 40
exercise workloads (64). An athlete who trains intensely for 12 weeks may experience a state 41
of ‘functional overreaching’, which is associated with a temporary performance decrement, 42
followed by improved performance. Intense training over an extended period without 43
sufficient balance between training and recovery may lead to ‘nonfunctional overreaching’ 44
(NFOR) (64). This condition is typically characterized by persistent fatigue, performance 45
decrement, muscle soreness, and psychological and hormonal disturbances that can last for 46

4
weeks or months. Depending on the time needed to recover from NFOR, an athlete may be 47
diagnosed (retrospectively) as experiencing ‘overtraining syndrome’ (64). 48
Recognition of the link between excessive training and risk of illness has stimulated 49
interest in nutritional supplements and physical therapies to counteract immunodepression 50
and to restore immune function after exercise training. In this mini-review, we update the 51
current state of knowledge about the temporal changes in the immune system following 52
exercise; how repeated bouts of exercise on the same day, extended periods of intense 53
training, and sleep disruption influence the immune system; and the efficacy of various 54
strategies for restoring immune function after exercise. 55
56
LEUKOCYTE REDEPLOYMENT DURING EXERCISE AND RECOVERY 57
A single exercise bout causes profound changes in the number and composition of blood 58
leukocytes that may persist long into exercise recovery. All major leukocyte subpopulations 59
tend to increase in number during exercise as a result of hemodynamic shear stress and/or 60
catecholamines acting on leukocyte 
2
adrenergic receptors (126). The postexercise recovery 61
period is marked by opposite effects on blood neutrophil and lymphocyte numbers. 62
Neutrophil number (and, consequently, the total leukocyte count) often continues to increase 63
long into the recovery period (up to 6 h after exercise cessation), particularly if the exercise 64
bout is prolonged (>2 h) (86). This sustained ‘neutrophilia’ is characterized by an increased 65
presence of immature, less differentiated, precursor neutrophils in the blood (117), most 66
likely in response to the increased plasma levels of soluble agents including glucocorticoids, 67
growth hormone, and cytokines such as IL-6 and granulocyte colony-stimulating factor, which 68

Frequently asked questions

Q1. What are the contributions in "Recovery of the immune system after exercise" ?

The notion that prolonged, intense exercise causes an `` open window '' of immunodepression during recovery after exercise is well accepted this paper. 

Q2. What is the role of mTOR in leukocyte trafficking?

amino acid-sensitive mammalian target of 336rapamycin (mTOR) signaling is also a key mechanism underlying leukocyte trafficking (110). 

Q3. What is the role of exercise in preventing skeletal muscle damage?

Exercise is also known to mobilize 121hematopoietic stem cells, which may participate in skeletal muscle repair and regeneration 122after exercise (25, 49). 

Q4. What is the key to maintaining immune function after exercise?

A balanced and well-diversified diet that meets the energy demands in 447athletes and exercising individuals is certainly a key component to maintain immune function 448in response to strenuous exercise and intense periods of training. 

Q5. What are the phenotypes of lymphocytes that preferentially egress?

Lymphocyte subtypes that 92preferentially egress the peripheral blood during exercise recovery also have phenotypes 93consistent with tissue migration (e.g., expression of surface adhesion molecules, chemokine 94receptors) (108). 

Q6. What is the role of angiogenic T cells in recovery?

A 119recent study showed that acute exercise mobilizes angiogenic T cells, which may facilitate 120vascular remodeling during exercise recovery (53). 

Q7. What sites are likely to be used for effector lymphocytes?

These lymphocytes most likely translocate to peripheral sites of potential 95 antigen encounter, such as the lungs or the gut (48). 

Q8. How does the lymphocyte count after exercise decrease?

Following prolonged 74and/or high-intensity exercise in particular, lymphocyte number commonly decreases to 75below the preexercise value within as little as 30 min (126). 

Q9. What is the evidence that exercise redeploys 105T cells?

Recent evidence showing that exercise redeploys 105T cells that are specific to latent herpesviruses such as cytomegalovirus (CMV) and Epstein–106Barr virus (EBV) (111, 112) suggests that this response may be a countermeasure against 107stress-induced viral reactivation (107). 

Q10. What are the changes in the immune system in response to overreaching?

Neutrophil count, plasma cytokine concentrations, CD4:CD8 T-cell ratio, and salivary 193IgA concentration are more variable (or do not change) in response to functional overreaching 194(39, 95, 124). 

Q11. What is the effect of protein and leucine on the immune system after exercise?

Another study demonstrated that protein and leucine supplementation for 1–3293 h post-exercise during 6 d of high-intensity training enhanced neutrophil respiratory burst 330activity after the last exercise session (69). 

Q12. What is the effect of low carbohydrate intake on leukocytes during recovery?

Compared with a higher carbohydrate intake (8 g/kg/d), very low 301carbohydrate intake (0.5 g/kg/d) leads to greater perturbation in leukocyte subsets during 302recovery from exercise (65). 

Q13. What is the effect of a disrupted night’s sleep on the immune system?

Compared with normal sleep, a disrupted night’s sleep appears to 211prime the immune system and enhance immunosurveillance by stimulating total 212 lymphocytes, CD8+ 

Q14. What is the evidence that reduces immune cell function in vitro?

some evidence suggests that reduced immune cell function in vitro may 418 coincide with changes in vivo and rates of illness (14, 40). 

Q15. What is the evidence that NK cells and CD8+ 98T cells express?

recent evidence indicates that CD8+ 98T cells and NK cells mobilized by exercise do not express cutaneous homing receptors on their 99surface (121). 

Q16. What is the role of carbohydrate in reducing IL-6 release during exercise?

Although the systemic release 247of IL-6 during exercise is related to muscle glycogen depletion (114), the precise mechanism 248by which carbohydrate supplementation reduces systemic IL-6 release from contracting 249muscle during exercise is not clear, because carbohydrate supplementation does not alter 250 muscle glycogen content (75).