American Journal of Lifestyle Medicine
Moderate Exercise Improves
Immunity and Decreases
David C. Nieman, DrPH, FACSM
DOI: 10.1177/1559827610392876. Manuscript received April 30, 2010; revised June 1, 2010; accepted June 2, 2010. From the Department of Health and Exercise
Science, Appalachian State University, Boone, North Carolina. Address correspondence to David C. Nieman, DrPH, FACSM, Department of Health and Exercise Science,
PO Box 32071, 111 River St, HCC Room 38, Appalachian State University, Boone, NC 28608; e-mail: email@example.com.
For reprints and permissions queries, please visit SAGE’s Web site at http://www.sagepub.com/journalsPermissions.nav.
Copyright © 2011 The Author(s)
vol. x • no. x
Old age, avoidance of physical
activity, mental stress, poor nutrient
and energy status, and lack of sleep
have all been associated with
impaired immune function and
elevated risk of infection.
Abstract: Moderate exercise training
causes favorable perturbations in
immunity and a reduction in inci-
dence of upper-respiratory illness (URI).
During each bout of moderate exercise,
an enhanced recirculation of immu-
noglobulins, neutrophils, and natural
killer cells occurs that persists for up to
3 hours postexercise. This exercise-
induced surge in immune cells from
the innate immune system is tran-
sient but improves overall surveillance
against pathogens. As moderate exer-
cise continues on a near-daily basis for
12 to 15 weeks, the number of symptom
days with URI is decreased 25% to 50%
compared with randomized sedentary
controls. Epidemiological and animal
studies support this inverse relationship
between URI risk and increased physi-
cal activity. Recent evidence indicates
that maintaining leanness and a phys-
ically active lifestyle during adulthood
reduces systemic inflammation, an
underlying factor in multiple chronic
diseases. The anti-inflammatory influ-
ence of near-daily physical activity in
lowering C-reactive protein, total blood
leukocytes, interleukin-6, and other
inflammatory cytokines may play a key
role in lowering risk of cardiovascular
disease, certain types of cancer, type 2
diabetes, sarcopenia, and dementia.
Keywords: upper-respiratory-tract infec-
tion; physical activity; natural killer cells;
Upper-respiratory illness (URI) is the
most frequently occurring infectious
disease in humans worldwide.
than 200 different viruses cause the
common cold, and rhinoviruses and
coronaviruses are the culprits 25% to 60%
of the time. The US Centers for Disease
Control and Prevention has estimated that
more than 1 billion URIs occur annually
in the United States, a leading cause of
lost school and work days. The average
person has 2 or 3 respiratory infections
each year, with young children suffering
6 to 7. Non–influenza-related viral respi-
ratory infections impart an estimated
$40 billion burden in direct and indirect
costs on the US economy.
Lifestyle habits are strongly related to
immune function. Old age, avoidance
of physical activity, mental stress, poor
nutrient and energy status, and lack
of sleep have all been associated with
impaired immune function and elevated
risk of infection. For example, the
likelihood of getting ill is directly linked
to the magnitude and duration of stress-
ful events and demeanor.
6-month period, for example, the num-
ber of sick days is twice as great in
high- compared with low-stress groups.
Sleep disruption also impairs immune
American Journal of Lifestyle Medicine XXX • XXX XXXX
function. For example, the antibody
response to the flu shot is reduced in
individuals experiencing sustained sleep
In cold virus challenge studies,
thse with a history of poor sleep quality
were more prone to illness.
Nutrition has a major influence on
your immune function, and nearly
all nutrients provide support for the
immune system in its work against
viruses and bacteria. The best stud-
ies, however, indicate that a balanced,
healthy diet provides all the nutrients
needed for good immune function in
most healthy adults, and vitamin/mineral
supplements do not boost immunity
above normal levels.
In general, the
concept of boosting immune function
through improved lifestyle habits is
misleading. A better interpretation of
the literature is that a healthy lifestyle
supports normal immunity and that
poor habits of living impair immune
Low- to high-exercise workloads have
a unique effect on risk of URI. Regular
physical activity improves immune func-
tion and lowers URI risk, whereas sus-
tained and intense exertion has the
opposite effect. Figure 1 summarizes this
J-shaped-curve relationship. This article
will emphasize that each moderate exer-
cise bout causes immune system pertur-
bations that enhance immunosurveillance
against pathogens and at the same time
lowers risk of chronic disease by exerting
URI Risk, and
Several lines of evidence support the link
between moderate physical activity and
improved immunity leading to lowered
infection rates: survey, animal, epidemiolog-
ical, and randomized training data. Survey
data consistently support the common
belief among fitness enthusiasts that regular
exercise confers resistance against infection.
In surveys, 80% to 90% of regular exercis-
ers perceive themselves as less vulnerable
to viral illnesses compared with sedentary
peers, as summarized in Figure 2.
It is difficult to extrapolate animal
studies to the human condition, but in
general, they support the finding that
moderate exercise lowers morbidity and
mortality following pathogen inocula-
tion, especially when compared with
prolonged and intense exertion or physi-
cal inactivity. Mice infected with the her-
pes simplex virus, for example, and then
exposed to 30 minutes of moderate exer-
cise experience a lower mortality dur-
ing a 21-day period in contrast to higher
mortality rates after 2.5 hours of exhaus-
tive exercise or rest.
Epidemiological reports have retro-
spectively or prospectively compared
URI incidence in large groups of mod-
erately active and sedentary individu-
als. Collectively, the epidemiological
studies consistently show reduced URI
rates in physically active or fit individu-
als. A 1-year epidemiological study of 547
adults showed a 23% reduction in URI
risk in those engaging in regular versus
irregular moderate-to-vigorous physical
activity, as summarized in Figure 3.
In a group of 145 elderly people, URI
symptomatology during a 1-year period
was reduced among those engaging in
higher compared with lower amounts
of moderate physical activity.
1-year study of 142 men aged 33 to 90,
the odds of having at least 15 days with
URI was 64% lower among those with
higher physical activity patterns.
Project PRIME, a randomized clinical trial
that investigated interventions to increase
physical activity, the odds ratio for
reporting URI symptoms was 0.50 (95%
confidence interval = 0.28 to 0.91) among
participants who engaged in a minimum
of 150 minutes per week of moderate
and vigorous activity compared with less
A group of 1002 adults (ages 18 to
85 years, 60% female, 40% male) were
followed for 12 weeks (half during the
High Risk for
J-Curve Model on the Relationship
Between Exercise Workload, and Risk of
Upper-Respiratory-Tract Infection (URI).
Fewer Same Greater
Percentage of Runners (N = 226)
Cold Frequency Compared to Sedentary Peers
Survey Responses by WSER athletes in response to this question: “Compared
to others who do no run or exercise do you feel that you generally have
_____________ episodes of sickness with the common cold or ﬂu?” Data From
American Journal of Lifestyle Medicinevol. X • no. X
winter, half during the fall) while monitor-
ing URI symptoms and severity using the
Wisconsin Upper Respiratory Symptom
Participants reported frequency
of moderate-to-vigorous aerobic activity
and rated their physical fitness level using
a 10-point Likert scale. Figure 4 shows that
the number of days with URI was signifi-
cantly reduced by 43% in those reporting
an average of 5 or more days of aerobic
exercise (20 minute bouts or longer) com-
pared with those who were largely seden-
tary (≤1 day per week). This relationship
occurred after adjustment for important
confounders, including age, education
level, marital status, gender, BMI, and per-
ceived mental stress. The number of days
with URI was reduced by 46% when com-
paring those in the highest versus lowest
tertile for perceived physical fitness, even
after adjustment for confounders.
Regular physical activity may lower
rates of infection for other types of dis-
eases. For example, women who were
regular and active walkers had an 18%
lower risk of pneumonia compared with
women who walked the least.
same cohort, women who reported run-
ning or jogging more than 2 hours per
week had a significantly lower risk of
pneumonia compared with women who
spent no time running or jogging.
Randomized experimental trials have
provided important data in support of the
viewpoint that moderate physical activity
reduces URI symptomatology. In 1 ran-
domized, controlled study of 36 women
(mean age 35 years), those in the exer-
cise group walked briskly for 45 minutes,
5 days a week, and experienced one half
the days with URI symptoms during the
15-week period compared with the sed-
entary control group (5.1 ± 1.2 vs 10.8 ±
2.3 days; P = .039).
The effect of exercise training (five
45-minute walking sessions/wk at 60%-
75% maximum heart rate) and/or mod-
erate energy restriction (1200-1300 kCal
per day) on URI was studied in non-
obese, physically active women (N = 30)
and obese women (N = 91, body mass
index 33.1 ± 0.6 kg/m
) randomized to
1 of 4 groups: control, exercise, diet,
exercise and diet.
All participants self-
reported symptoms of sickness in health
logs, using a precoded checklist. Energy
restriction had no significant effect on URI
incidence, and those from the 2 exercise
groups were contrasted with those from
the 2 nonexercise groups. The number
of days with symptoms of URI for those
in the exercise groups was reduced rela-
tive to the nonexercise groups (5.6 ± 0.9
and 9.4 ± 1.1 sickness days, respectively),
similar to that of the nonobese, physically
active controls (4.8 ± 0.9). Figure 5 sum-
marizes the combined data set from these
2 training studies.
A 1-year randomized study of 115 over-
weight, postmenopausal women showed
that those who had regular moderate exer-
cise (166 minutes per week, ~4 days per
week) had lowered URI risk compared
with controls (who engaged in a stretch-
In the final 3 months of
the study, the risk of colds in the control
group was more than 3-fold that of the
exercise group, as summarized in Figure 6.
During moderate exercise, several pos-
itive changes occur in the immune sys-
Moderate exercise increases the
recirculation of immunoglobulins, and neu-
trophils and natural killer cells, 2 cell types
that play a critical role in innate immune
defenses. Animal data indicate that lung
macrophages play an important role in
mediating the beneficial effects of moder-
ate exercise on lowered susceptibility to
Stress hormones, which can
suppress immunity, and pro-inflammatory
and anti-inflammatory cytokines, indica-
tive of intense metabolic activity, are not
elevated during moderate exercise.
Although the immune system returns to
preexercise levels within a few hours after
the exercise session is over, each session
represents a boost in immune surveillance
that reduces the risk of infection over the
long term. Other immune-related benefits
of exercise include enhanced antibody-
specific responses to vaccinations. For
example, several studies indicate that
both acute and chronic moderate exer-
cise training improve the body’s antibody
response to the influenza vaccine.
1 study, a 45-minute moderate exercise
bout just before influenza vaccination
improved the antibody response.
These data provide additional evi-
dence that moderate exercise favorably
influences overall immune surveillance
against pathogens. Taken together, the
data on the relationship between mod-
erate exercise, enhanced immunity, and
lowered URI risk are consistent with
guidelines urging the general public to
engage in near-daily brisk walking.
for Elderly People
Immune senescence or age-associated
immune deficiency is partly responsible
for some of the afflictions of old age.
Sedentary Low-Moderate High-Moderate High
URTI, Incidence Rate Ratio
Physical Activity Level
This 1-Year Study of 547 Adults Showed a 23% Reduction in Upper-
Respiratory-Tract Infection (URTI) Risk in Those Engaging in Regular Versus
Irregular Physical Activity. Data From Reference 11.
American Journal of Lifestyle Medicine XXX • XXX XXXX
URI (days during 12 week period)
StressAge Exercise Education Marital Sex BMI
The Number of Days With Upper-Respiratory Illness (URI) During a 12-Week Period (Winter or Fall) in a Group of 1002 Adults
(Ages 18 to 85 Years) by Various Lifestyle and Demographic Factors. Means Are Adjusted Statistically After Weighting for Each
Factor Through a General Linear Model. Data From Reference 15.
(N = 61)
(N = 65)
Days With URI Over 12 Weeks
The Number of Upper-Respiratory
Illness (URI) Symptom Days Was
Decreased by Approximately Half
Through a Walking Program (5 Days
Per Week, 45 Minutes Per Session, for
15 Weeks) by Previously Sedentary,
Overweight Adult Women. Data
Combined From References 18 and 19.
0 to 3 3 to 6 6 to 9 9 to 12
Number of Colds, Group Average
Every 3 Months
A 1-Year Randomized Study of 115 Overweight, Postmenopausal Women Showed
That 166 Minutes Per Week (~4 d/wk) of Moderate Exercise Lowered Upper-
Respiratory Illness Risk Compared With Controls (Stretching), Especially During the
Past 3 Months. Data from reference 20.
Elderly persons are more susceptible to
vaccine failure and many infections, auto-
immune disorders, and cancers when
compared with younger adults. The age-
related decline is most apparent in
T cell–dependent immune functions and
is related to thymus involution.
Aging is a complex process that ulti-
mately leads to irreversible biologi-
cal changes. However, health habits
can have a sizable influence on life
expectancy and quality of life, even in
A new and growing area of
research is the relationship between
certain lifestyle factors (in particular,
physical activity and diet) and immune
Older adults exercise less and have
lower levels of cardiorespiratory fitness
than younger adults, and recent stud-
ies indicate that this may contribute to
American Journal of Lifestyle Medicinevol. X • no. X
immune senescence. Acute and chronic
physical activity has a major influence
on various measures of immune func-
tion in older adults according to studies
conducted during the past 2 decades.
Although research on the role of endur-
ance exercise on the immune systems of
elderly human subjects is just beginning,
data from the few available studies are
intriguing and have potential for wide-
spread public health influence.
Several cross-sectional studies have
compared immune function in highly
conditioned and sedentary elderly
(ie, ≥65 years) men and women.
study contrasted immune function in
30 sedentary elderly women and 12 age-
matched, highly conditioned elderly
women (mean age, 73 years) who were
active in state and national senior game
and road race endurance events.
highly conditioned elderly women (aver-
of 31 mL
) had been
physically active for an average of 11 years
and had trained an average of 1.6 hours
daily during the previous year. The
highly conditioned participants exhibited
superior function of natural killer and T
lymphocytes compared with the 30 sed-
entary elderly women (Figure 7).
Another study compared immune func-
tion in 17 elderly runners, who had
trained for about 17 years, and 19 elderly
controls, and reported significantly higher
T lymphocyte function in the elderly run-
The elderly runners, when com-
pared with the elderly controls, also
demonstrated significantly higher rates
of interleukin-2 (IL-2), interferon-g, and
IL-4 production from activated T cells.
Another cross-sectional study of 13 sed-
entary and 13 physically active and
physically fit older adults (ages 60-76
years) revealed an augmented antibody
response to the flu vaccine.
Randomized exercise training stud-
ies have investigated the response of the
aging immune system to 2 to 6 months of
In 1 study, 30 sed-
entary elderly women (mean age, 73
years) were assigned to walking or sed-
The exercise group
walked 30 to 40 minutes, 5 days per
week, for 12 weeks at 60% heart rate
reserve; 12 weeks of moderate cardiore-
spiratory exercise improved the VO
(ie, maximum aerobic fitness) of the pre-
viously sedentary elderly participants by
12.6% but did not result in any chronic
improvement in natural killer or T cell
function relative to the sedentary con-
trol group. Incidence of URI in the highly
conditioned, walking, and calisthenic
control groups was compared during
the 12-week study (September through
November). Half of the elderly women in
the calisthenic group suffered a URI dur-
ing the study as compared with 3 of 14
women in the walking group and 1 of
12 in the highly conditioned group (c
= 6.36; P = .042; Figure 8). Thus, elderly
women not engaging in cardiorespira-
tory exercise were more likely than their
exercising counterparts to experience URI
during the fall season. Although the initi-
ation of moderate exercise by the elderly
did not alter chronic immunity, the acute
and transient immune changes during
each exercise bout may have improved
overall immunosurveillance, decreasing
the risk of URI.
A 10-month exercise training study
showed that the antibody titer response
to the influenza vaccine was increased in
elderly adults who had undergone train-
ing as compared with sedentary controls
(Figure 9). Those who exercised trained
at 65% to 75% heart rate reserve, 25 to
30 minutes, 3 days per week. Another
10-month training study with elderly par-
ticipants showed a significant reduction
in inflammatory measures, including IL-6,
C-reactive protein (CRP), and IL-18 com-
pared with controls.
These data add to
the growing consensus that moderate
exercise training helps improve vaccine
efficacy and counter chronic low-grade
inflammation in the elderly.
Collectively, these data from studies of
elderly participants provide good support
for the role of regular physical activity
T Cell Function (lymphocyte
proliferative response, CPM)
Natural Killer Cell Function
T Cell Function (A) and Natural Killer Cell Function (B) in Highly Conditioned
Female, Elderly Athletes Compared With Age- and Gender-Matched Sedentary
Controls. Data From Reference 44.
Walking Group Control Group
URI Incidence Over 12 Weeks (% group)
Upper-Respiratory Illness (URI)
Incidence in 3 Groups of Elderly
Women During 12 Weeks: Highly
Conditioned, Walkers, and Controls.
Data From Reference 44.
American Journal of Lifestyle Medicine XXX • XXX XXXX
as therapy against immune senescence.
Physical activity has acute and chronic
beneficial effects on the immune systems
of elderly people. Cross-sectional studies
of highly active, highly conditioned, rela-
tively lean elderly men and women indi-
cate that T cell function is superior to that
of their sedentary peers but still below
the levels of untrained, young adults.
Several 2- to 6-month training studies
(both resistance and endurance exercise)
have shown that elderly persons can sig-
nificantly improve strength and aero-
bic fitness, lower URI rates, and improve
vaccine efficacy but without meaningful
changes in chronic immune function.
These data suggest that each moder-
ate exercise bout by elderly participants
causes temporary but positive improve-
ments in immunosurveillance that improve
host protection and vaccine antibody
responses. Research on the acute effects
of moderate exercise suggest that both
young and old adults recruit immune cells
in a similar fashion, and this increased
recirculation of cells may enhance immu-
nosurveillance when physical activity is
conducted on a near-daily basis.
on Inflammation and
Acute inflammation is a normal response
of the immune system to infection and
trauma. Chronic, low-grade inflammation,
however, is linked with multiple disor-
ders and diseases, including atheroscle-
rosis and cardiovascular disease (CVD),
the metabolic syndrome, diabetes mel-
litus, sarcopenia, arthritis, osteoporosis,
chronic obstructive pulmonary disease,
dementia, depression, and various types
CRP is the most frequently
measured inflammatory biomarker, and
individuals with CRP values in the upper
tertile of the adult population (>3.0 mg/L)
have a 2-fold increase in CVD risk com-
pared with those with a CRP concentra-
tion below 1.0 mg/L.
Large population observational stud-
ies show reduced serum CRP and other
inflammatory biomarkers (eg, the white
blood cell count, IL-6, and tumor necrosis
factor [TNF]-a) in adults with higher lev-
els of physical activity and fitness.
One Month Three Months
Mean Fold Increase in Influenza
Elderly Controls Exercise Group Young Controls
Comparison at 1 and 3 Months of Antibody Response to the Inﬂuenza Vaccination in
Elderly Controls, Elderly Exercisers, and Young Controls. Data From Reference 27.
Serum CRP (mg/L, adjusted mean anti-log)
BMI Gender Exercise
The Inﬂuence of Aerobic Exercise Frequency and Other Lifestyle and Demographic
Factors on C-Reactive Protein (CRP). Means Are Adjusted Statistically After Weighting
for Each Factor Through a General Linear Model. Data From Reference 61.
inverse association between physical
activity/fitness with inflammation is
related in part to the effect of activity
on fat mass.
In most studies, however,
adjustment for adiposity attenuates but
does not negate the strength of the rela-
tionship between inflammatory biomark-
ers and physical activity/fitness.
In a recent study of 1002 community-
dwelling adults (age range, 18- 85 years),
a general linear model analysis adjusted
CRP means for frequency of physical
activity, BMI, and several other lifestyle
and demographic factors (Figure 10).
As summarized in Figure 10, BMI had the
strongest effect on CRP followed by gender,
American Journal of Lifestyle Medicinevol. X • no. X
exercise frequency, age, and smoking
An elevated fasting IL-6 concentration
is a significant component of the chronic
low-grade inflammation that underlies the
metabolic syndrome, CVD, diabetes, and
During prolonged exer-
cise, IL-6 is produced by muscle fibers
and stimulates the appearance in the cir-
culation of other anti-inflammatory cyto-
kines such as IL-1ra and IL-10.
inhibits the production of the proinflam-
matory cytokine TNF-a and stimulates
lipolysis and fat oxidation.
loss from energy restriction and exercise,
plasma levels of IL-6 fall, skeletal mus-
cle TNF-a decreases, and insulin sensitiv-
Thus, IL-6 release from
the exercising muscle may help mediate
some of the health benefits of exercise,
including metabolic control of type 2 dia-
Muscle IL-6 release, however, is
very low during moderate physical activ-
ity, and additional research is needed to
determine if other exercise-induced fac-
tors mediate the anti-inflammatory influ-
ence of regular physical activity.
By far, the most important finding that
has emerged from exercise immunology
studies during the past 2 decades is that
positive immune changes take place during
each bout of moderate physical activity.
Over time, this translates to fewer days of
sickness with the common cold and other
URIs. These data are strengthened by sev-
eral lines of evidence across both animal
and human studies. The 25% to 50% reduc-
tion in sick days with near-daily moderate
exercise exceeds levels reported for most
medications and supplements and bolsters
public health guidelines urging individuals
to be physically active on a regular basis.
The anti-inflammatory effect of near-
daily physical activity may play a key
role in many health benefits, includ-
ing reduced CVD, type 2 diabetes, var-
ious types of cancers, sarcopenia, and
dementia. This is an exciting area of sci-
entific endeavor, and additional research
is needed to determine how immune
perturbations during each exercise bout
accumulate over time to produce an anti-
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