EVIDENCE OF THE EFFECT OF EXERCISE THERAPY

ON IMMUNITY
The capability of the human body to resist almost all types of organisms
or toxins that tend to damage the tissues and organs is called immunity. [1]
The immune system is traditionally divided into two different branches the adaptive immune system, the arm of the immune system that mounts
a specific response to foreign antigens, and the innate immune system. [2]
Acquired immunity does not develop until after the body is first attacked
by a bacterium, virus, or toxin, often requiring weeks or months to
develop the immunity. Innate immunity results from general processes,
rather than from processes directed at specific disease organisms. [1] The
immune system may be detailed as-: [3]
Table 1: Main elements of the immune system [3]
Innate components
Adaptive components
Cellular

Cellular

Natural killer cells (CD 16+,

CD56+)
Phagocytes (neutrophils,
eosinophils, basophils,
monocytes, macrophages)

Soluble

T cells (CD3+, CD4+,

CD8+)
B cells (CD19+, CD20+,
CD22+)

Soluble

Acute phase proteins

Complement
Lysozymes
Cytokines (interleukins,
interferons, colony-stimulating
factor, tumour necrosis factors)

Immunoglobulins IgG, IgA,

IgD, IgE, IgM
Memory

Over the past years, a variety of studies have demonstrated that exercise
induces a considerable physiological change in the immune system. The
interactions between exercise stress and the immune system provide a
unique opportunity to link basic and clinical physiology. [4] In essence, a
bout of exercise induces mobilization of immunocompetent cells to the
circulation. [5]

Comparison of immune function in athletes and nonathletes reveals that

the adaptive immune system is largely unaffected by athletic endeavour.
It is the innate immune system which appears to respond differentially to
the chronic stress of intensive exercise, with natural killer cell activity
tending to be enhanced while neutrophil function is suppressed. [6]

Major findings of practical importance in terms of public health and

athletic endeavour include: [7]
i.

In response to acute exercise, natural killer (NK) cells, neutrophils,

and macrophages (of the innate immune system) appear to be most
responsive to the effects of acute exercise, both in terms of
numbers and function. [7]

ii.

In response to long-term exercise training, significant elevation in

NK cell activity is seen but there is some indication that neutrophils
function is suppressed during periods of heavy training. [7]

iii.

Limited data suggest that unusually heavy acute or chronic exercise

may increase the risk of upper respiratory tract infection (URTI),
while regular moderate physical activity may reduce URTI
symptomatology. [7]

iv.

Work performance tends to diminish with most systemic infections,

and clinical case studies and animal data suggest that infection
severity, relapse, and myocarditis may result when patients exercise
vigorously. [7]

v.

Although regular exercise has many benefits for HIV-infected

individuals, helper T cell counts and other immune measures are not
enhanced significantly.[7]

vi.

Data suggest that the incidence and mortality rates for certain types
of cancer are lower among active subjects. The role of the immune
system may be limited, however, depending on the sensitivity of the
specific tumor to cytolysis, the stage of cancer, the type of exercise
program, and many other complex factors. [7]

vii.

As individuals age, they experience a decline in most cell- mediated

and humoral immune responses. Two human studies suggest that
immune function is superior in highly conditioned versus sedentary
elderly subjects. [7]

Athletes who are undergoing heavy training regimens should realize that
each of these factors has the potential to compound the effect that
exercise stress is having on their immune systems. [7]
Thus, this essay covers these above mentioned points in details to
understand the effect of exercise or exercise therapy on immunity in
athletes along with some evidence in the non-athletic population in terms
of the chronic illnesses.

Immune Functions in Sports

Exercise can have both positive and negative effects on immune function
and susceptibility to minor illnesses. The relationship between exercise
and susceptibility to infection has been modelled in the form of a Jshaped curve. This model suggests that, while engaging in moderate
activity may enhance immune function above sedentary levels, excessive
amounts of prolonged, high intensity exercise may impair immune
function. [8] The adaptive immune system (resting state) in general seems
to be largely unaffected by intensive and prolonged exercise training. The
innate immune system appears to respond differentially to the chronic
stress of intensive exercise.[6]

Figure 1: The J-Shaped Model

[9]

However, one study gave an extended relationship of the J-shaped model;

in the elite athletes suggesting the relationship is S-shaped postulating
that previous infections, pathogen exposure, and other stressors than
exercise may also influence the infection outcome. Observed infections in
athletes can, therefore, be either the result of increased susceptibility to a
novel pathogen, or more severe symptoms of an already established
infection. [10

Figure 2: The
Model [10]

S-Shaped

Retrospective and prospective longitudinal studies have identified that the

majority of elite athletes experience symptoms of URTI at a rate similar to
the general population, however, the episodes of URTI in elite athletes do
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not follow the usual seasonal patterns of URTI but rather occur during or
around competitions. Symptoms occur more frequently during the high
intensity training and taper period prior to competitions in some sports,
such as swimming and kayaking, while in other endurance sports, such as
long distance running, URTI symptoms appear more frequently in the
athletes after a competition. [9]
Pyne and colleagues, for example,
reported that elite swimmers
undertaking intensive training had a
significantly lower neutrophil oxidative
activity at rest than age- and gendermatched sedentary individuals, and
that function was further suppressed
during the period of strenuous training
prior to national-level competition.
Nonetheless, upper respiratory tract
infection rates did not differ between
the swimmers and sedentary control
individuals. [6]

Figure 3: The Comparison of the

Swimmers and Sedentary Controls for
the Neutrophil Function [6]

Acute Immune Response to Exercise Training

After a period of brief strenuous exercise following changes are seen in the
immune function. [4]

Figure 4: The Effect of Strenuous Exercise on Immune Function

[4]

Figure 5: The Effect of Strenuous Exercise on Cytokines

[14]

Several authors have suggested that prolonged cardio respiratory

endurance exercise leads to transient but clinically significant changes in
immune function. During this open window of altered immunity (which
may last between 3 and 72 hours, depending on the immune parameter
measured as well as the type, duration and intensity of exercise), viruses
and bacteria may gain a foothold, increasing the risk of subclinical and
clinical infection. [6]
The open window theory is characterised by short term suppression of
the immune system following an acute bout of endurance exercise. This
window of opportunity may allow for an increase in susceptibility to upper
respiratory illness (URI). [11]
Ten male A grade cyclists exercised for two hours at 90% of their second
ventilatory threshold. Blood samples were collected pre-, immediately
post-, 2 hours, 4 hours, 6 hours, 8 hours, and 24 hours post-exercise.
Immune variables examined included total leukocyte counts, neutrophil
function , lymphocyte subset counts , natural killer cell activity (NKCA),
and NK phenotypes . This is the first study to show changes in
immunological variables up to 8 hours post-exercise, including significant
NK cell suppression, NK cell phenotype changes, a significant increase in
total lymphocyte counts, and a significant increase in eosinophil cell
counts all at 8 hours post-exercise. Suppression of total lymphocyte
counts, NK cell counts and neutrophil phagocytic function following
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exercise may be important in the increased rate of URI in response to

regular
intense endurance training [11].

Figure 6: Immune System after Heavy, Prolonged Exertion

The production of secretory immunoglobulin A (SIgA) is the major effector

function of the mucosal immune system providing the first line of
defence against pathogens. To date, the majority of exercise studies have
assessed saliva SIgA as a marker of mucosal immunity but more recently
the importance of other antimicrobial proteins in saliva (e.g. -amylase,
lactoferrin and lysozyme) has gained greater recognition. Acute bouts of
moderate exercise have little impact on mucosal immunity but prolonged
exercise and intensified training can evoke decreases in saliva secretion of
SIgA. [9]
A study conducted to determine the effects of high-intensity endurance
exercise on skin immunity by estimating secretory immunoglobulin A
(SIgA) and staphylococci on skin surface. Seven healthy adult men
performed bicycle exercise at 75% HRmax for 60 minutes from 2030 to
2130 hours. Secretory immunoglobulin A was obtained from 1 ml
extraction liquids stirred with the microtube homogenizer in the open end
of a polypropylene tube for 60 seconds. Skin surface samples were
collected from the chest and the forearm. Secretory immunoglobulin A
concentration on the forearm was significantly lower than on the chest
The number of staphylococci was significantly higher on the forearm. The
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study concluded that high-intensity endurance exercise might depress

immune function and enhance infectious risk on skin surface. Coaches
should encourage their athletes to take a shower and change into clean
clothes immediately after sports activities and athletes should maintain a
clean skin surface to decrease the infectious risk on skin surface. [12]
In the true resting state (i.e. more than 24 h after their last training
session) circulating lymphocyte numbers and functions appear to be
broadly similar in athletes compared with non-athletes. In contrast, T and
B cell functions appear to be sensitive to increases in training load in well
trained athletes undertaking a period of intensified training, with
decreases in circulating numbers of Type 1 T cells, reduced T cell
proliferative responses and falls in stimulated B cell Ig synthesis reported.
The cause of this depression in acquired immunity appears to be related
to elevated circulating stress hormones, particularly cortisol, and
alterations in the pro/ anti-inflammatory cytokine balance in response to
exercise. This appears to result in a temporary inhibition of Type 1 T cell
cytokine production with a relative dampening of the Type 1 (cellmediated) response. [9]
Chronic Exercise and Immune Response
The immune function (resting levels) in athletes compared with nonathletes has more similarities than disparities, as reviewed.Natural
immunity may be slightly increased, whereas neutrophil function has been
reported to be slightly suppressed. The adaptive immune system (resting
state) in general seems to be largely unaffected by intensive and
prolonged exercise training. The innate immune system appears to
respond differentially to the chronic stress of intensive exercise, with NK
cell activity tending to be enhanced while neutrophil function is
suppressed. [14]
Moderate Exercise and Immune Response
Nieman et al. examined the effect of 15 weeks of moderate-intensity
exercise training on symptoms of URTI. Exercising subjects demonstrated
shorter infectious episodes compared to their sedentary controls as
measured by number of symptom-days per infectious episode. In addition,
URTI symptom-days were negatively-correlated with increases in fitness.
[13]

It is the Th1 response which is essential in combating the viral infection.

Of particular importance is IL-12 which bridges the gap between innate
and adaptive immunity by driving the differentiation of nave T helper
cells (Th0) toward a Th1 phenotype characterized by the production of
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pro-inflammatory cytokines IL-2 and IFN-. Th1 secreted IL-2 promotes the
maturation of antigen specific cytotoxic T-lymphocytes (CD8+ T cells)
which recognize viral antigens on infected cells through the association of
major histocompatibilty complex (MHC) I interactions with T cell receptors
(TCR). Prolonged Th1 activity, however, may lead to respiratory tissue
pathology, through increased cell damage and necrosis. Immune counterregulatory mechanisms attempt to prevent Th1 induced pathology by
shifting the Th cell phenotype towards Th2, characterized by the secretion
of anti-inflammatory proteins IL-4 and IL-10. [13]

Effect of Exercise Therapy on Immunodeficiency Disorders or

Inflammatory Conditions or Aging
It is generally believed that immune function undergoes degenerative
changes with aging. This immune senescence potentially engenders an
increased susceptibility to infectious diseases, malignancy, and
autoimmune disorders in elderly people. By this immunosenescence, as
the thymus involutes, T cells, which play a central role in cellular immune
function, show the largest age-related alterations in distribution and
function. [15]
Twenty-four elderly subjects were assigned to an exercise training group
or a non-exercise control group. Subjects in EXC participated in exercise
sessions 2 d_wk for 12 weeks. Subjects in CON maintained their normal
physical activity levels during the study period. The study concluded that
exercise training in elderly people is associated with increased CD28expressing Tc cells and CD80-expressing monocytes. Therefore, exercise
training might upregulate monocyte and T-cell-mediated immunity in
elderly people. [15]
Chronic diseases are the largest cause of death in the world, led by
cardiovascular disease followed by cancer, chronic lung diseases, and
diabetes mellitus. Regular exercise offers protection against all-cause
mortality, primarily by protection against atherosclerosis, Type 2 diabetes,
colon cancer, and breast cancer. In addition, physical training is effective
in the treatment of patients with ischemic heart disease, heart failure,
Type 2 diabetes, and chronic obstructive pulmonary disease. [16]
The initial cytokines in the cytokine cascade are (named in order) TNF-,
IL-1, IL-6, IL-1 receptor antagonist (IL-1ra), and soluble TNF-_ receptors
(sTNFR). Chronic low-grade inflammation accompanies aging as well as
some chronic medical disorders. During aging, increased plasma levels of
TNF-, IL-6, IL-1ra, sTNF-R, and CRP have been demonstrated. Given that
low-grade systemic inflammation is found in patients with obesity, insulin
resistance, Type 2 diabetes, and atherosclerosis The first two cytokines in
the cytokine cascade are TNF- and IL-1, which are produced locally.
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These cytokines are usually referred to as pro-inflammatory cytokines.

TNF- and IL-1 stimulate the production of IL-6, which has been classified
as both a pro- and an anti-inflammatory cytokine. The cytokine response
to exercise differs from that elicited by severe infections. The fact that the
classic pro-inflammatory cytokines, TNF- and IL-1, in general do not
increase with exercise indicates that the cytokine cascade induced by
exercise markedly differs from the cytokine cascade induced by infections.
Typically, IL-6 is the first cytokine present in the circulation during
exercise. The level of circulating IL-6 increases in an exponential fashion
(up to 100-fold) in response to exercise and declines in the post-exercise
period. [16]

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Figure 7: In sepsis (A), the cytokine cascade within the first few hours consists
of TNF-, IL-1, IL-6, IL-1ra, TNF-R, and IL-10. The cytokine response to
exercise (B) does not include TNF-_ and IL-1 but does show a marked increase
in IL-6, which is followed by IL-1ra, TNF-R, and IL-10. Increased CRP levels
do not appear until 812 h later.

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In conclusion, regular exercise protects against diseases associated with

chronic low-grade systemic inflammation. This long-term effect of exercise
may be ascribed to the anti-inflammatory response elicited by an acute
bout of exercise. [16]
Also, epidemiological evidence exists that supports the anecdotal
impression1 that regular exercise increases resistance to infections such
as the common cold, whereas hard training is associated with increased
upper respiratory tract infections. Also, there is accumulating evidence
that exercise is a lifestyle that offers some protection against malignancy.
It has become clear that moderate exercise stimulates the immune
system and may be somewhat responsible for exercise related reduction
in illness. However, strenuous exercise induces immunosuppression in the
recovery period and may explain the increased risk of infection in
athletes. [14]

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7. D. C. Nieman, Exercise Immunology: Practical Applications, Int J

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Nobuhiko Eda, Kazuhiro Shimizu, Satomi Suzuki, Yoko Tanabe,
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Stephen A. Martin, Brandt D. Pence, Jeffrey A. Woods, Exercise
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Aizawa,Hideyuki Nanba,Yukichi Hanaoka,Shinya Kuno,Noboru
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