Accepted Manuscript

Title: Establishing a Dose-Response Relationship Between

Acute Resistance-Exercise and the Immune System: Protocol
for a Systematic Review

Authors: Adam Michael Szlezak BBiomedSc., DPT Dr. Siri

Lauluten Szlezak AEP, BSportSci., MSportSc., PhD Dr. James
Keane B.Sc., PhD Dr. Lotti Tajouri BSc, MSc, PhD A/Prof Dr.
Clare Minahan BApplSci, BExSci(Hons.), PhD Dr.

PII: S0165-2478(16)30243-7
DOI: http://dx.doi.org/doi:10.1016/j.imlet.2016.10.010
Reference: IMLET 5942

To appear in: Immunology Letters

Received date: 16-6-2016

Revised date: 2-10-2016
Accepted date: 30-10-2016

Please cite this article as: Szlezak Adam Michael, Szlezak Siri Lauluten, Keane
James, Tajouri Lotti, Minahan Clare.Establishing a Dose-Response Relationship
Between Acute Resistance-Exercise and the Immune System: Protocol for a Systematic
Review.Immunology Letters http://dx.doi.org/10.1016/j.imlet.2016.10.010

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Establishing a Dose-Response Relationship Between Acute Resistance-Exercise and the Immune
System: Protocol for a Systematic Review

Authors
Dr Adam Michael Szlezak, BBiomedSc., DPT (Corresponding Author) a
E: dr.szlezak@gmail.com

Dr Siri Lauluten Szlezak, AEP, BSportSci., MSportSc., PhD b

E: siri.szlezak@gmail.com

Dr James Keane, B.Sc., PhD b

E: keanejames4@gmail.com

A/Prof Dr Lotti Tajouri, BSc, MSc, PhD b

E: ltajouri@bond.edu.au

Dr Clare Minahan, BApplSci, BExSci(Hons.), PhD a

E: c.minahan@griffith.edu.au

Corresponding author contact details:

E: dr.szlezak@gmail.com
T: +617 5552 7842
F: +617 5552 8674

a
Griffith Sports Physiology, Griffith University, Parklands Drive, Southport QLD 4215, Australia
b
Faculty of Health Sciences & Medicine, Bond University, Robina QLD 4226, Australia
 Highlights

A bout of resistance-exercise induces acute changes in leukocyte counts

High-dose exertions appear to cause more rapid responses
Low-dose exertions appear to cause smaller, and or delayed responses
The timing of measures relative to the onset of exercise needs to be reported
A dose-response relationship appears to exist for resistance-exercise & leukocytes

Abstract

Exercise immunology research has traditionally focussed on aerobic-exercise, however it has become
apparent in more recent years that resistance-exercise can also considerably affect host
immunobiology. To date however, no systematic process has been used to establish a dose-response
relationship between resistance-exercise and the immune system. The present systematic review was
thus conducted to determine the dose-response effects of a bout of resistance-exercise on acute
leukocyte counts. In accordance with the PRISMA guidelines, a systematic literature search was
conducted in the electronic databases, PubMed, Web of Science, and Google Scholar, over the date
range of 1989-2016. Following the PICO elements, eligibility criteria included: i) participants: healthy
humans aged 18-40; ii) intervention: a single bout of resistance-exercise; iii) comparator: at least one
comparator group; iv) outcome: acute measures of circulating leukocyte counts. Specific exclusion
criteria was also applied. Risk of bias and quality of evidence was assessed using the PEDro scale.
Due to the individual designs of the admitted studies, a qualitative analysis (systematic narrative
synthesis) was employed in the present review. The results of the present review demonstrate that a
single bout of resistance-exercise induces an acute monocytosis, neutrophilia, and lymphocytosis. It
became apparent that the reviewed literature either does not consistently specific, or describe with
sufficient detail, the time-course between the onset of exercise and the collection of blood. We
recommend that researchers consider addressing this in future studies, and also collect blood measures
during exercise to aid with comparison of temporal effects. Regarding the determination of a dose-
response relationship, an acute neutrophilia, monocytosis and lymphocytosis appears to occur more
rapidly and to a greater magnitude following a single bout of high-dose vs low-dose resistance-
exercise. Mechanistically, exercise-induced trafficking changes are associated with mechanical,
metabolic and endocrine factors. Physical aptitude of the host may also affect resistance-exercise-
induced lymphocyte trafficking responses.

Keywords: Exercise dose-response; Exercise intensity; Immune response; Leukocytes; Lymphocytes;

Resistance exercise
1. Introduction

The link between the immune system and exercise in athlete health, tissue repair, and regeneration and
coordination of other adaptive processes has become a prominent area of focus in the Sports Science
and Medicine communities since the formation of the International Society of Exercise and
Immunology (ISEI) in 1989 [1, 2]. Both acute and chronic-exercise intervention studies have reported
significant responses in terms of leukocyte redistribution/trafficking, activity and function [2]. The
immune responses to exercise are not disorganised or random, and specific cells are redistributed for
defined functional purposes [3]. Traditionally, exercise immunology research has employed aerobic-
exercise, and found a general consensus that an acute bout of aerobic-exercise induces a transient
neutrophilia, monocytosis and lymphocytosis [2]. Of relevance to the practice of exercise prescription,
key exercise protocol variables, exercise intensity and duration/volume, have been reported to
influence the redistribution of cells into the circulation associated with exercise [2, 4-6].

A developing body of research is now emerging which describes the effects of resistance-exercise on
host immunobiology. This literature has primarily focused on the post-exercise redistribution of
leukocytes following high-dose resistance-exercise protocols [3, 7, 8]. Similar to aerobic-exercise, a
single bout of resistance-exercise has been reported to induce an acute neutrophilia [9, 10],
monocytosis [11, 12] and lymphocytosis [9, 13]. Additionally, these changes in leukocyte trafficking
appear to be regulated by the dose of resistance-exercise [3, 9, 14, 15] in a manner analogous to that of
aerobic-exercise [2]; that is, increasing the dose may affect the leukocyte response, thus a systematic
examination of this dose-response notion is warranted. Despite preliminary investigation, significant
basophil [13, 16] and eosinophil [13,16] trafficking changes have not been found, suggesting a less
substantial role may exist for these cells in response to exercise-induced stress. However, it must be
noted that basophils and eosinophils have acted as investigation targets in far fewer exercise studies
than other leukocytes [3, 14]. Furthermore, basophils specifically have received relatively minimal
attention across all subfields of experimental immunology [17].

Now that a sufficient amount of preliminary data has been reported through well conducted resistance-
exercise studies, it is evident that researchers have been biased in their selection of exercise dose.
Exercise dose comprises intensity (%-1RM [one-repetition maximum]), recruited muscle-mass (cross-
sectional area [CSA] of active muscle), volume (reps x sets), duration (time-under-tension [s]), and
rest periods (recovery between sets [s]). The existing literature is primarily composed of studies which
administered varying degrees of high-dose (i.e., high-volume and or intensity, large muscle-mass)
resistance-exercise [3, 13, 18], and thus less is known about the influence of low-dose (i.e., low-
volume and or intensity, small muscle-mass) resistance-exercise on acute leukocyte counts. Few
studies, such as our recent works [14, 15], have examined the influence of very low-dose resistance-
exercise on host immunobiology. Nonetheless, these low-dose studies also demonstrate significant
acute changes to leukocyte trafficking following resistance-exercise. Whilst the functional
implications of resistance-exercise induced modulation of the immune system are unclear, existing
data [12-15] provide strong evidence that resistance-exercise, like aerobic-exercise, disrupts leukocyte
homeostasis.

Pragmatically, exercise immunology has the potential to reveal novel and safe methods of
manipulating host leukocyte activity and function. Resistance-exercise could therefore be prescribed
like a pharmacological agent, and as such, establishing a dose-response relationship between
resistance-exercise and the immune system will be fundamentally important. As with the field of
pharmacology, which studies the minimum dose of a drug required to produce a given effect (dose-
response [19]), exercise immunology must also examine the consequences of low and micro-doses of
resistance-exercise.

With regard to the central role of leukocytes in both host-defence and physiological adaptation [20,
21, 22], the primary aims of this systematic review are to: i) provide an update on the known acute
leukocyte cell trafficking/redistribution responses to resistance-exercise in resistance-trained and
untrained participants; ii) examine the doses of exercises which have been used in the current
literature to assist in establishing a dose-response relationship between resistance-exercise and the
immune system. Knowledge of this relationship could ultimately assist in enhancing the safety of
exercise participation, improve exercise outcomes, and direct the way in which exercise can be
prescribed to benefit an individuals health status. The secondary aim of this review is to describe the
potential mechanisms underlying the acute leukocyte trafficking changes associated with resistance-
exercise.

2. Methods

The present systematic review follows the recommendations of the Preferred Reporting Items for
Systematic Review and Meta-Analysis Protocols (PRISMA-P) 2015 statement [23].

2.1. Search Strategy and Information Sources

A systematic literature review was conducted across the date range, January 1989 to August 2016,
using the online databases PubMed, Web of Science, and Google Scholar. Google Scholar was used as
an adjunct database, due to its well-documented utility as a uniquely thorough literature search tool,
including for the identification of relevant grey literature [24-26].The following search terms (and
Medical Subject Heading [MeSH] of the United States National Library of Medicine [NLM]) were
used in PubMed and Web of Science: (resistance training)OR "(resistance exercise" OR "weight
training" OR "strength training") AND ("leukocyte" OR "monocyte" OR "granulocyte" OR
"lymphocyte" OR leukocytosis OR lymphocytosis OR "B cell" OR "T cell"). Additional limits
(PubMed) were set as follows: human; age - birth-18yr; 19-44yr; language English; date range
1989-2016; full text.

Google Scholar was searched using the following terms (With all of the words): "resistance
exercise" OR "resistance-exercise" AND "leukocyte" AND "leukocyte count" AND "exercise intensity"
OR "intensity of" OR "exercise dose" OR "dose of". Additional limits were set as follows: yrs 1989
2016; Not including patents or citations .

2.2. Eligibility and Selection Criteria

Once the literature search was complete, search results were assessed to determine their suitability for
inclusion into the present review. Preliminary assessment involved reviewing the titles and abstracts
of each manuscript. Where the title or abstract explicitly demonstrated that the study was outside the
scope of the present review, and or that eligibility criteria were not satisfied, the manuscript was not
considered further. In the event that the title or the abstract of a manuscript did not indicate the studys
potential eligibility for inclusion, the full-text article was examined. The manuscript in question was
then flagged as either potentially eligible, or ineligible. To guarantee that all eligibility criteria were
satisfied, articles deemed potentially eligible during database searching were assessed by two
reviewers (AMS and SLS) and their consensus statement was used. The exclusion criteria were also
considered and implemented by the two reviewers. In accordance with the PICO elements [23], study
eligibility (inclusion) criteria comprised: (a) population: healthy human participants (male and female)
aged 18-40, resistance-exercise trained and or resistance-exercise untrained; (b) intervention: a single
bout of resistance-exercise administered at high- and or low-doses; (c) comparator: at least one
comparator group (e.g., non-active control group or another group who performed resistance-
exercise); (d) outcome: acute measures of circulating leukocyte counts, either during or post a bout of
resistance-exercise. Studies were excluded if they: (a) did not indicate the following fundamental
components of exercise dose regarding their exercise interventions; (i) intensity; (ii) volume; (iii)
specific exercises performed (as an indication of recruited muscle-mass); (b) included both aerobic
and resistance-exercise components; (c) employed other interventions in addition to the resistance-
exercise (e.g., supplementation).

2.3. Data Collection Process and Data Items

For those manuscripts which were accepted into the present review, data was extracted and inserted
into a table using standard word-processing software (Microsoft Word, WA, USA). Data was
extracted in accordance with the PICO elements [23] (see Eligibility and Selection Criteria).
Specifically, the following data points were extracted: (i) author and year of publication; (ii) gender;
(iii) subject groups, sample size and age; (iv) exercise mode; (v) intensity and volume; (vi) rest
periods; (vii) time-under-tension; (viii) timing of blood collection (from onset of exercise); (ix)
exercise(s) performed/protocol; (x) key cell counts measured and cognate findings.
2.4. Outcomes and Prioritisation

The primary outcomes of the included studies were acute measures of circulating leukocyte counts
(combined or individual subpopulations), before and after a bout of resistance-exercise. Changes in
cell count/concentration (absolute or relative) as well as the timing of these changes (temporal
response) were the priority. Non-exercise control group data (where available) was also included for
comparison.

2.5. Risk of Bias and Quality of Evidence Assessment

The risk of bias, as well as the quality of evidence of individual studies included in the present review,
was assessed by two reviewers (AMS and SLS) using the Physiotherapy Evidence Database (PEDro)
scale [27]. The PEDro scale covers the themes of randominsation, concealment of allocation,
similarity of key measures at baseline, blinding, attrition/bias in results, intention to treat, and
quality of statistical methods employed. The scale encompasses 11 items with 3 items from the Jadad
scale [28] and 9 items from the Delphi list [29]. The PEDro scale score is then calculated from 0 (low
quality) to 10 (high quality), with a score of 6 representing a cut-off for high-quality studies [27, 30].
However, it has also been reported that reducing the cut-off score to 5 (or even 4) does not reduce the
quality of evidence [27, 31]. It should be noted that the first item (regarding external validity) of the
PEDro scale is not included in scoring [30]. Fair-to-good inter-rater reliability has been reported for
the PEDro scale [27].

2.6. Qualitative Analysis

Due to the: a) degree of heterogeneity among designs of the included studies (e.g., post-exercise time-
points; exercise protocol variables), and; ii) the lack of data describing when blood was collected
relative to the onset of exercise (see Results and Discussion), it was not appropriate to perform a
quantitative analysis of study findings. Consequently, a systematic narrative synthesis was used with
information presented in the text and Table 1 to summarise and explain the characteristics and
findings of the included studies. The narrative synthesis was then used to describe, where possible, a
dose-response relationship between resistance-exercise and acute leukocyte counts. In order to
undertake this narrative synthesis, a combined results and discussion section was necessary.

2.7. Publication and Outcome Reporting Bias

Publication and outcome reporting bias was assessed by examining all included manuscripts to
confirm that planned leukocyte count outcomes (as per the methods sections) were reported as results
in the results sections [23, 32].
3. Results and Discussion: Specific Cell Responses to Resistance-Exercise

The database searches yielded a combined total of 345 results (PubMed, n=46; Web of Science, n=88;
Google Scholar, n=211). Initial assessment of the title and abstract (or full-text, where appropriate) of
each manuscript resulted in the exclusion of 281 manuscripts. These manuscripts were either not
appropriate (see Eligibility and Selection Criteria) or represented duplicate search results. Of the
remaining 64 manuscripts which were subjected to the eligibility and exclusion criteria, 16 were
admitted into the present review.

No evidence was found to indicate that publication bias or outcome reporting bias had occurred in any
of the admitted studies. Overall PEDro score (n=16; meanSD) was calculated as 51.3, indicating
fair-strength/quality of evidence. Of note, no study admitted in the present review scored below 4/10,
thus supporting the calculated strength of the reviewed studies [27, 31]. Regarding the description of
the exercise interventions featured in the reviewed literature, it became evident during data extraction
that authors did not consistently report time-under-tension, and when this was reported, precise
descriptions were often lacking. It was also noted that the literature does generally not report, or
describe with precision, the time-course between the onset of exercise and blood sampling.
Consequently, Table 1 does not include data describing time-under-tension or timing of blood
sampling relative to the onset of exercise.

Regarding the overall findings of the present review, the majority of the literature which has
investigated the acute effects of resistance-exercise on leukocytes has focussed on changes in cell
count in the circulation [3, 9, 13-15, 33]. The exercise-training status (physical aptitude) of
participants who were recruited in existing studies ranged from untrained to recreationally resistance-
trained, to competitive weightlifting-trained [3, 14, 15]. A systematic narrative synthesis of the
findings from this review, as they relate to establishing a dose-response relationship (resistance-
exercise and acute leukocyte counts), is presented as follows:

3.1. Monocytes

Monocytes are cellular precursors to tissue macrophages which are essential in tissue regeneration,
repair and recovery through processes including phagocytosis and promotion of myosatellite cell
stimulation [34, 35]. Monocytes therefore represent a cell population of fundamental importance for
both innate immune function, and recovery from resistance-exercise. There is general agreement in the
literature that an acute bout of resistance-exercise induces an acute monocytosis, which occurs during
and or following exertion [9, 11-14, 33, 36]. Following high-dose resistance-exercise, monocyte
values have been reported to return to baseline between 15-30-min post exertion [13] or peak at 120-
min post exercise cessation (final time-point [33]). The discrepancy between these temporal profiles
may be due to differences in exercise dose, however this is unlikely since intensities and volumes
were not substantially dissimilar (see Table 1). It is thus possible that differences in blood collection
time-points relative to the onset of exercise, as well as the use of dissimilar post-exercise time-points,
create an apparent discrepancy. Due to an inconsistency among the selection of terminal post-exercise
time-points in existing studies [13, 33], currently it is only possible to conclude that resistance-
exercise induces a monocytosis. Of note, shorter rest intervals (1-min vs 3-min) are reportedly
associated with a greater response magnitude [9]. The exercise protocols employed in the current
literature have consistently been of a high-dose, ranging from 2 sets of a circuit (75%-1RM: 10
different exercises [33]) to single large muscles groups with high-volume (10 x 10 reps at 65%-1RM:
leg press [9]) and result in a rapid monocytosis, evident immediately-post exertion. One study which
administered a relatively lower dose of resistance-exercise (low-intensity, high-volume vs high-
intensity, low-volume [37]) reported no change in monocyte count following lengthening (eccentric)
contractions of the elbow flexors. The only report of monocyte responses to a very low-dose of
resistance-exercise [14] conversely showed a delayed monocytosis (at 60-min post exercise) following
low-intensity, low-volume (thumb) resistance-exercise. It is unclear as to why elbow flexor exertion
failed to induce a monocytosis where thumb exertion did, however it could be that baseline fitness
levels of the different muscle groups (and therefore the magnitude of physiological strain incurred) is
an influencing factor. In regards to the dose-response relationship of monocytes following resistance-
exercise, a bout of high-dose exercise appears to induce an acute monocytosis during exercise,
whereas a bout of low-dose exercise appears to induce a delayed acute monocytosis (following
exercise). This suggestion supports the notion that increased exercise intensity and duration augment
the leukocyte responses to resistance-exercise [3, 9]. One caveat to this idea which must be noted
however, is that low-dose exercise is generally short in duration (e.g., 5-10-min). Consequently, a
delayed post-exercise cell count change (e.g., 60-min post exercise) following a low-dose exertion
could represent the same absolute time-point as a cell count change following a high-dose intervention
which lasted 60-min. The current literature does not consistently report exercise duration (total or
time-under-tension) or the amount of time (min or h) between the onset of exercise and the blood
collection time-points. This notion applies to all subtypes of circulating leukocytes, not just
monocytes, and is only noted in this section of the present review for the purpose of maintaining
concise reporting. Future researchers are strongly encouraged to collect blood during exercise, as well
as describe in detail the time-course of their data collection (time from onset of exercise to blood
extraction) and duration of their resistance-exercise protocols so that the influence of resistance-
exercise dose on circulating leukocyte counts can be irrefutably established.

3.2. CD4+ T Cells

T helper/inducer lymphocyte subpopulations possess diverse functionality including activation and

regulation of immunological events in both the innate and adaptive (humoral and cell-mediated)
divisions of the immune system [20]. Several subtypes of T helper/inducer cells exist (Th1, Th2,
Th17, T follicular helper cells) and can be differentiated phenotypically through analysing their
cytokine profiles and cell-surface cluster of differentiation (CD) markers [20]. The differences in
cytokine profiles of CD4+ cell subtypes relate to their distinct functional roles, and thus differential
analysis of the CD4+ subpopulations in exercise studies is preferable to a grouping of all CD4+ cells.
For example, Th1 cells function in eliminating intracellular pathogens and are also associated with
organ-specific autoimmunity [38]. Conversely, Th2 cells mount responses to extracellular parasites, as
well as regulate inflammatory activity indirectly through secretion of the cytokine IL-4, which
promotes pro-inflammatory action through IL-6, GM-CSF (granulocyte-macrophage colony-
stimulating factor), and the cell adhesion molecule VCAM-1 (vascular cell adhesion molecule 1) [39].
Th2 cells can also negatively regulate inflammation through the secretion of the master regulator
cytokine, IL-10 [40], hence differential analysis of CD4+ cell subtypes is necessary in order to study
the physiological implications of exercise-induced changes in CD4+ cell homeostasis.

Current studies which reported T helper/inducer cell responses to resistance-exercise did not perform
assays which allow differentiation of individual CD4+ cell subtypes (Th1, Th2, Th17, T follicular
helper cells) [11-13, 15, 33]. Additionally, the reported CD4+ T cell responses to resistance-exercise
vary in the literature. A CD4+ lymphocytosis has been shown to exist immediately following high-
dose (75%-1RM at different volumes) resistance-exercise [11, 13, 33], or develop between 0-60-min
following very low-dose resistance-exercise [15]. CD4+ T cell counts have been reported to: return to
baseline within 30-min following a high-dose exertion (untrained) [13], or within 60-min following a
low-dose exertion (untrained) [15]; or remain elevated at 60-min (final time-point) succeeding a low-
dose exertion (resistance-trained) [15]. Of note, the lower-dose resistance-exercise produced a smaller
magnitude response than higher-dose protocols [3, 15]. In contrast to an exercise-induced
lymphocytosis, one study [12] reported no change in CD4+ T cell count (despite an increase in total
lymphocytes) following an upper and lower body resistance-exercise protocol (60-70%-1RM). The
latter study did not however collect blood between 0-min post and 3-h post exercise, thus a potential
change in cell count could have occurred but was not observed. Additional studies which examine
CD4+ T cell responses to low-doses of resistance-exercise are needed to assist in accurately
establishing a dose-response profile for resistance-exercise and CD4+ T cells. However, examination
of the current literature indicates that a bout of high-dose resistance-exercise induces a relatively
larger CD4+ T cell lymphocytosis which occurs during exercise, whereas a bout of lower-dose
resistance-exercise [12, 15] induces a smaller and delayed acute CD4+ T lymphocytosis (or no
change).

3.3. CD8+ T Cells

CD8+ cytotoxic T cells are central to resistance against intracellular pathogens [41]. Accordingly, an
understanding of how resistance-exercise affects this subpopulation is of high relevance to the health
maintenance of an exercising individual. The literature on CD8+ T cell count responses to resistance-
exercise groups CD8+ (suppressor and cytotoxic) T cell subpopulations together. A CD8+ T cell
lymphocytosis has been reported to exist immediately succeeding high-dose (60-75%-1RM at
different volumes) resistance-exercise [11-13], or develop from 0-60-min post very low-dose
resistance-exercise relative to training status [15]. Following high-dose resistance-exercise, CD8+ T
cell count reportedly returns to pre-exercise levels by 15-min succeeding exercise [13] or decreases
below pre-exercise levels [33] by 30-min of rest, and is at baseline values by 3-h post exercise [12].
Possible reasons for the differences in observed responses (return to baseline vs decrease below
baseline) may relate to slight variances in exercise volume, or differences in the timing of blood
collections relative to the onset of exercise. Of note, the study which reported a decrease in CD8+ T
cell count [33] also observed a return to pre-exercise levels by 120-min following exercise cessation.
The authors of this latter study suggested that regular resistance-exercise could increase susceptibility
to infection, however insufficient evidence exists to support this notion presently. In contrast to the
studies which employed high-dose exercise protocols, our recent very low-dose study [15] reported
that CD8+ T cell count returned to baseline between 20-60-min post exercise in untrained subjects,
but remained elevated (60-min post; final time-point) in resistance-trained individuals. Of note,
response magnitudes were lower than previously reported in high-dose exercise studies, further
supporting the notion that leukocyte responses are regulated by exercise dose (namely volume and
intensity) in a positive direction. Currently, the clinical implications of CD8+ T cell responses to
resistance-exercise require considerable investigation. Considering that high-doses of resistance-
exercise may have both positively and negatively directed regulatory effects on CD8+ T cell
trafficking, further research is necessary to assist in elucidating the potential clinical implications of
resistance-exercise on host immune defence against intracellular pathogens [41]. Regarding the dose-
response relationship between resistance-exercise and CD8+ T cells, further data is needed which
describes the response of this subpopulation to low-dose resistance-exercise. Based on the existing
evidence however, it appears that a bout of high-dose resistance-exercise induces an acute CD8+ T
cell lymphocytosis during exercise, and a potential transient decrease in cell count following exercise
before returning to baseline. Conversely, a bout of low-dose resistance-exercise appears to induce a
delayed acute lymphocytosis, which is influenced by training status.

3.4. CD19+ B Cells

In addition to their role in humoral immunity and antibody secretion, B cells are also critical in
initiating T cell mediated immune responses [42]. B lymphocyte counts may be measured through
assessing cell-surface expression of CD markers such as CD19 (denoting young immature and mature
cells) and CD20 (a mature B cell-specific molecule) [42]. To date, CD19+ B cells have been the focus
in research examining leukocyte responses to resistance-exercise. There has been a consistent
reporting of an elevated CD19+ B cell count in the circulation following high-doses (60-100%-1RM
at different volumes; [11, 12, 18] and very low-doses of resistance-exercise [15]. A bout of high-dose
resistance-exercise appears to induce a CD19+ B cell lymphocytosis which occurs either during
resistance-exercise [11, 18], or after resistance-exercise (evident after 3-h rest) [12]. The reason for the
discrepancy in temporal responses is unknown, however may relate to the differences in exercise
volumes among studies, and the fact that only one high-dose study [12] recorded measures beyond
immediately-post exercise. Of note, the amount of total-work performed during a bout of resistance-
exercise (in high- vs low-strength individuals) can reportedly influence the CD19+ B cell response
[18]. That is, only high total-work (i.e., high-dose) has been shown to result in a significant cell count
elevation [18]. This latter point must be considered with caution however, since low total-work may
be equally challenging for low-strength individuals as high total-work is for high-strength individuals.
Currently, no data is available which describes a return-to-baseline time-course for CD19+ B cells
following high-dose resistance-exercise. Similar to the effects of a high-dose exertion, our recent
study [15] reported a CD19+ B cell lymphocytosis by 20-min (untrained) and 60-min (resistance-
trained) succeeding a very low-dose bout of resistance-exercise. Response magnitude was lower than
reported for high-dose exertions [15]. Moreover, CD19+ B cell values had returned to baseline by 60-
min (rest) in untrained subjects only. Of note, this dichotomous response (relative to training status)
was consistent with that observed for CD4+ and CD8+ T cells following the same exercise dose [15]
suggesting that training status may influence the dose-response relationship for these lymphocytes if
exercise doses are low. The mechanisms underlying this observation are currently unknown and
require investigation. No effect of training status was reported with high-dose exercise [11]. Studies
are currently lacking which report on the response of CD20+ B cells to exercise. Since co-expression
of CD19+ and CD20+ markers can occur during B cell development [42], studies should ideally
measure both CD markers to determine which subpopulations are present in their samples. Further
studies are now recommended which employ low and high-dose resistance-exercise protocols for
comparison. These studies should assay for multiple CD markers including but not limited to CD19,
CD20, and CD23 (as an indicator of B cell activation [42]) to determine the effects of resistance-
exercise on B cells at different developmental and functional stages. Regarding the dose-response
relationship between resistance-exercise and CD19+ B cells, bouts of both high- and low-dose
resistance-exercise can be said to induce an acute lymphocytosis which occurs either during or
following exercise. Furthermore, the response magnitude appears to be augmented by increasing the
exercise dose. Conversely, further research is needed before it is possible to determine how the dose
of exercise affects the temporal response of CD19+ B cells since the current data is inconsistent.

3.5. CD16+/56+ NK Cells

CD16+/56+ NK cells have received significant attention in the exercise-immunology literature, likely
since they are an easily studied target cell, and their response-magnitude is substantial [2]. These
innate cytotoxic lymphocytes are primarily known to induce cell death of infected cells and
characteristically secrete interferon-gamma [43]. The well documented NK cell response to a bout of
resistance-exercise is an acute lymphocytosis which is observable immediately succeeding exercise
[11-13, 18, 33]. This response profile is based on high-dose (60-100%-1RM at different volumes)
resistance-exercise. The CD16+/56+ NK cell count can be sustained up to 15-min post-exercise before
returning to baseline by 30-min [13], or it may decrease below baseline by 30-min following exercise
[33]. Additionally, CD16+/56+ NK cell count has been reported to re-establish baseline values by 3-h
post exercise [12]. Although exercise intensities and volumes varied slightly among the high-dose
studies, the discrepancy among results may be explained by the differences in blood collection time-
points relative to the onset of exercise, and the use of different post-exercise time-points. In contrast to
a lymphocytosis, we found no change in CD16+/56+ NK cell count [15] following a very-low-dose
bout of resistance-exercise. However, our first measurement was not taken until 20-min post-exercise,
thus it is possible that a potential response could have occurred and renormalised prior to assessment.
Additional low-dose studies recording measures immediately-post exercise are now indicated to assist
in establishing a dose-response relationship between resistance-exercise and the functionally
important CD16+/56+ NK cell. Studies should also perform repeated measures over a protracted
recovery time course to determine if the NK cell count returns to baseline or diminishes below
baseline. It should be noted that the magnitude of change in cell count was reportedly not associated
with total-work performed in one study [18]. A caveat with this finding however is that total-
workloads were performed relative to strength levels (e.g., high-strength = high total-work), and thus
it is unknown whether absolute physiological strain was similar or different between groups due to the
differences in strength. Consequently, further data is needed to determine the specific impact of
manipulating resistance-exercise dose on CD16+/56+ NK cell count, regarding both the response
magnitude and temporal profile.

3.6. Neutrophils

Like CD16+/56+ NK cells, neutrophils have been a popular cell type to examine in resistance-exercise
immunology studies. Neutrophils, a member of the granulocytes which aid macrophages with
phagocytosis and oxidative burst activity [44], respond to a bout of high-dose resistance-exercise with
an acute neutrophilia occurring either during or following exertion [9, 10, 12, 13, 33, 36, 37, 45, 46].
Following a bout of high-dose resistance-exercise (see Table 1), a neutrophilia may remain elevated
[12, 13, 33] and peak up to 3-h post exercise [46]. Of note, a neutrophilia can occur more rapidly
following a bout of lower-intensity/higher-volume (80%-1RM, 5x10 reps) vs higher-intensity/lower-
volume (100%-1RM, 15x1 reps) resistance-exercise [36]. It is not presently possible to determine
exactly why post-exertional temporal profiles vary for neutrophils in the literature. As previously
stated however, there is a need for researchers to report when there measures occurred relative to the
onset of exercise. It must be noted that two high-dose studies have reported no change in neutrophil
cell count, however neither of these studies obtained measures beyond 5-min post-exercise [16, 47].
Since the time at which a post-exertional neutrophilia can occur is variable, these latter negative
findings are not inconsistent with other data. In contrast to the studies which utilised high-doses of
resistance-exercise, only two studies have utilised lower-doses of resistance-exercise. A neutrophilia is
reported to occur by 3-h post eccentric elbow flexor exercise, which of note, does not differ between
maximal vs submaximal exertion [37]. Recently, we reported no change in neutrophil count within 60-
min post-exercise [14] providing further evidence that resistance-exercise induced neutrophilia, like
that from aerobic-exercise [2, 5], is governed by exercise dose.

From a clinical perspective, preliminary neutrophil functionality studies indicate that an acute bout of
aerobic-exercise can increase the degranulation, phagocytosis and oxidative burst activity of
unstimulated neutrophils [2, 5, 48, 49]. However, recently mobilised cells (through exercise) may
demonstrate attenuated granulation and oxidative burst activity in response to exogenous stimuli such
as bacteria during the recovery period [5, 48, 49]. Considering that resistance-exercise can also
mobilise neutrophils, resistance-exercise induced neutrophilia may acutely enhance host innate
immune function, yet adversely affect function during the recovery period. Further investigations are
now needed which examine both low and high-doses of resistance-exercise. These studies will lead to
safer outcomes for exercising individuals regarding susceptibility to infection, and inform the way in
which exercise can be prescribed to enhance innate immune function. Regarding the dose-response
relationship between resistance-exercise and neutrophils, it appears that a bout of high-dose
resistance-exercise induces a neutrophilia either during or following exertion. A more rapid response
may also occur by increasing the exercise volume. Following a bout of lower-dose resistance-exercise,
either no change or a delayed neutrophilia appears to occur, however further low-dose examinations
are needed to confirm this.

3.7. Basophils

Basophils, best known for their role in hypersensitivity responses as effector cells, feature scarcely in
the exercise-immunology literature [17]. This is probably due to the limited focus and attention that
these granulocytes have received in general immunology research until very recently [17, 50]. The
current literature is yet to report a significant change in basophil count post a bout of resistance-
exercise, despite employing high-dose [13, 16] and low-dose [14] resistance-exercise protocols in
trained and untrained participants. Conversely, recent research developments in general immunology
have suggested a potential immune-regulatory role for basophils through histamine release and
subsequent upregulation of anti-inflammatory cytokine (IL-10) expression [17, 51]. It may therefore
be that basophils have a greater role in chronic vs acute exercise-induced leukocyte responses.
Considering that changes in local and systemic inflammatory status is a consequence of resistance-
exercise [37, 52], future studies should assess acute basophil responses in populations who perform
habitual resistance-exercise, such as resistance-trained athletes, and include untrained participants for
comparison. Competitive weightlifting-trained participants were recruited in our recent study on this
basis [14], however the extremely low-dose of exercise which was administered may have been
insufficient to elicit a potential basophil response.

3.8. Eosinophils

Eosinophils, the third member of the granulocyte family, have primarily been implicated in the
pathobiology of allergy [53, 54]. Their potential role in recovery from exercise remains unknown,
however as their trafficking is promoted through Th2 cell activity (indirectly through the Th2
cytokines IL-4, IL-5 and IL-13 [55-57]) and the fact that Th2 cells are affected by resistance-exercise,
eosinophils represent a cellular target warranting further investigation.

Generally, there has been no reported elevation in eosinophil numbers within 30-min post a bout of
high-dose resistance-exercise [13, 16]. Our recent work [14] measured eosinophil responses to a very
low-dose of resistance-exercise; nevertheless, no change in cell count was reported in either trained or
untrained participants.

4. Metabolic Influences on Leukocyte Responses to Resistance-Exercise

Existing studies indicate that a positive correlation exists between exercise-dose and leukocyte
responses, thus increasing the dose will augment the response [3, 9, 14]. Conversely, preliminary data
suggests that lymphocytes may respond through a unique mechanism. One notable study [11] reported
that acute exercise-induced increases in CD16+/56+ NK cells, CD4+, CD8+ and CD19+ B
lymphocyte counts were related to the highest compared with the lowest post-exercise lactate levels.
The authors of this research in turn reported that anaerobic intensity (indicated by blood lactate
levels) was associated with the magnitude of exercise induced lymphocytosis [11]. From a
mechanistic perspective, this relationship between anaerobic intensity (indicated by blood lactate
levels) and lymphocyte subpopulation counts was not seen in the granulocytes or monocytes,
indicating that a selective redistribution had occurred. Recently, we [15] examined the potential
relationship between exercise induced changes in blood lactate and lymphocyte subpopulations
(CD16+/56+ NK cells, CD4+, CD8+ and CD19+ B cells) following a bout of very low-dose
resistance-exercise. Our investigation found no relationship between blood lactate and lymphocyte
profiles, however a clear trend was identified between B and T lymphocyte responses and exercise-
training status of the host. The discrepancy in findings between the two studies which examined blood
lactate may relate to the differences in magnitude of reported blood lactate elevations.
Mechanistically, it is plausible that blood lactate selectively regulates lymphocyte trafficking at larger
[11] blood lactate elevations only, justifying the need for further research which co-investigates high
and low-dose resistance-exercise protocols.
5. Leukocyte Redistribution Mechanisms Relevant to Resistance-Exercise

Mechanical factors such as shear force have been reported to strongly affect leukocyte redistribution
from the marginated pool into the circulation, however, catecholamines also appear mechanistically
involved [58, 59]. Resistance-exercise is known to increase circulating catecholamines (adrenalin)
which are influenced by exercise protocol variables such as dose and intensity [60, 61]. The adrenalin
ligand can then bind to its cognate cell-surface adrenergic receptor on a target cell, notably, the 2
Adrenoceptor. Since lymphocytes phenotypically express a high cell-surface density of 2 Adrenergic
receptors, they represent a susceptible target to exercise-induced modulation via adrenaline [62]. In
the event of catecholamine binding to these cognate receptors, lymphocytes (primarily) would be
redistributed from the marginated pool, into the circulation through increased cellular Cyclic
Adenosine Monophosphate (cAMP) levels and subsequent signal transduction pathways which
promote reduced endothelial wall cell-adhesion [63, 64]. cAMP may also aid in tissue localisation of
cells [63]. Since 2 Adrenoceptor cell-surface expression varies significantly among leukocyte
subpopulations [62], leukocyte responses to resistance-exercise likely occur in a highly coordinated
and selective manner that is mediated through adrenalin.

It has been reported that the magnitude of catecholamine release during exercise is strongly associated
with training status [61], moreover the lymphocyte cell-surface density of 2 Adrenoceptor has been
shown to increase with both exercise and exposure to catecholamines [65]. Of note, an association
between blood lactate and exercise-induced catecholamine change has also been reported [66]. These
reports collectively suggest that specific lymphocyte responses and sensitivity to resistance-exercise
could vary significantly depending on the dose of exercise employed, and the physical aptitude of the
exercising individual.

6. Conclusions

The acute immune responses to a single bout of resistance-exercise represent sensitive and
coordinated cellular regulatory events which have a transient yet substantial influence on leukocyte
trafficking, and potentially cell functionality. A single bout of resistance-exercise has been shown to
consistently induce a transient monocytosis, neutrophilia, and lymphocytosis where responses appear
to be positively regulated by exercise dose, specifically intensity and duration variables. A transient
reduction may also occur in circulating CD16+/56+ NK and CD8+ T cells following resistance-
exercise. It is not known whether these decreases are clinically relevant, be it favourable or
deleterious, and thus require further investigation before conclusions can be drawn. Currently the
limited number of studies which have examined eosinophils and basophils suggest a lesser role exists
for these cell types in responding to exercise induced stress. There is an evident bias in the literature
towards employing high-dose exercise protocols when examining the effects of resistance-exercise on
host immunobiology. Additionally, existing studies either generally do not report, or are imprecise in
their reporting of the timing of blood collection relative to the onset of exercise. Knowledge of this
data is needed to accurately compare the results of distinct studies, and in turn establish a
comprehensive dose-response relationship between resistance-exercise and changes in leukocyte
subpopulation counts. Researchers are encouraged to include this information in their future works, as
well as consider collecting blood samples during exercise which will allow for better comparison of
temporal effects among studies.

In considering the results of this systematic literature review, an overall PEDro score of 5 (1.3) was
calculated, indicating fair-strength/quality of evidence. Based on this sufficient level of
methodological quality, the following dose-response relationship conclusions can be made: i)
Monocytes: a bout of high-dose resistance-exercise appears to induce an acute monocytosis during
exercise, whereas a bout of low-dose resistance-exercise appears to induce a delayed acute
monocytosis (following exercise); ii) CD4+ T cells: a bout of high-dose resistance-exercise induces a
relatively larger CD4+ T cell lymphocytosis which occurs during exercise, whereas a bout of lower-
dose resistance-exercise induces a relatively smaller and delayed acute CD4+ T lymphocytosis (or no
change); iii) CD8+ T cells: a bout of high-dose resistance-exercise appears to induce an acute CD8+ T
cell lymphocytosis during exercise, and a potential transient decrease in cell count following exercise,
before returning to baseline. In contrast, a bout of low-dose resistance-exercise appears to induce a
delayed acute lymphocytosis; iv) CD16+/56+ NK cells: resistance-exercise induces a rapid acute
lymphocytosis, however further data is needed to determine the effect of manipulating exercise dose
on CD16+/56+ NK cell count; v) Neutrophils: a bout of high-dose resistance-exercise induces a
neutrophilia, either during or following exertion, and a more rapid response may be associated with
greater exercise volume. A bout of lower-dose resistance-exercise, results in either no change or a
delayed neutrophilia, however further low-dose examinations are needed to confirm this; vi) Basophils
and eosinophils: resistance-exercise does not appear to affect acute cell counts at either high- or low-
doses, however further research is needed to confirm this.

Regarding the potential mechanisms underlying leukocyte count changes associated with resistance-
exercise, sheer stress and catecholamines likely represent mechanical and physiological mechanisms,
respectively, which promote cell redistribution. Further studies examining a wider range of exercise
doses combined with cell trafficking parameters and functionality assays are now needed to reveal
clinically insightful data which could assist in improving the safety of exercise participation, exercise
recovery outcomes, and health status.

Conflict of Interest

The authors declare no conflict of interest.

Author Contributions

AMS conceived the manuscripts theme, developed the search strategy, drafted the manuscript and is
the guarantor. AMS and SLS developed the eligibility and selection criteria, selected the risk of bias
assessment strategy and data extraction criteria. CM and SLS provided expertise on the exercise
interventions. JK and LT provided expertise on the leukocyte cell types. All authors read, provided
feedback, and approved the final manuscript.

Acknowledgements

No funding was received for the present project.

Vitae

Dr Adam M Szlezak, BBiomedSci., DPT

Dr Adam Szlezak is an Integrative Biologist and a registered Physiotherapist (Australia). He received

his DPT from Bond University, and is currently in the thesis examination stage of his PhD candidature
(Integrative Biology). A key focus of Dr Szlezaks research is the effect of resistance-exercise on the
immune system, cellular biology, and behavioural neuroscience, for the purpose of enhancing the safety
and efficacy of exercise. Dr Szlezak has also published research in the clinical health sciences.

Dr Siri L Szlezak, AEP, BSportSci., MSportSc., PhD

Dr Siri Szlezak is a Sports Scientist and an Accredited Exercise Physiologist (Australia). A primary
focus of Dr Szlezaks research is the examination of the multidimensional nature of training monitoring
in athletes and exercising individuals. This includes the links between molecular level events and
physiological parameters indicative of human performance potential, as well as the role of the immune
system in training monitoring.

Dr James Keane, B.Sc., PhD

Dr James Keane received his PhD from Bond University in 2013. His primary research focus has been
on examining the effects induced by hormones, such as growth hormone and IGF-1, on mitochondrial
physiology. His research has yielded publications in the fields of metabolism, immunology, rheology
and exercise science.

A/Prof Dr Lotti Tajouri, BSc, MSc, PhD

Dr Lotti Tajouri is an Associate Professor at Bond University, Australia, in the field of molecular
genetics. Having undertaken his Bachelor and Masters level degrees in France, he completed his PhD
thesis in molecular genetics at Griffith University, funded by a prestigious Lindsay Yeo Research
Scholarship. His research has examined gene profiling in a range of medical conditions, including breast
cancer, multiple sclerosis, rheumatoid arthritis, leukaemia and migraines; resulting in numerous
published articles and conference presentations.

Dr Clare Minahan, BApplSci, BExSci(Hons.), PhD

Clare Minahan is a Senior Lecturer in Sports Science at Griffith University on the Gold Coast, Australia.
Her research interests are in sport performance enhancement via exercise and mindfulness training, as
well as nutritional (sodium bicarbonate, caffeine, beta-alanine) and environmental (simulated altitude)
interventions. A key focus of Dr Minahans research is the effect of hormonal contraception on athletic
performance.

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Table 1: Characteristics of included studies

Author(s) Gender Groups & Intensity Volume Rest Type Exercise Key Cell Key Findings
& Year Age (sets x Periods Protocol Count
(yrSD) reps) Measures

Dohi et al. W All UT: 100%-10RM 6 x 10 2-min Full body Squat CD16+/56+ CD16+/56+ and
2001 High- cells, CD19+ CD3+ cells by 0-min
strength, cells, CD3+ CD19+ by 0-min
n=8 cells post in high-strength
(23.62.6) (grouped T group only
cells)
vs *High-strength
Low- performed more total
strength, work than low-
n=8 strength
(21.43.5)
Ghanbari- M 35%-1RM 35%-1RM 3 circuit 1-min Circuit 10 different LE, LY, NE No change with
Niaki et al. (19.850.5 CON: No rounds; rest exercises: Biceps exercise
2013 5) exercise 20-s per between with barbell, sit-
exercise rounds up, triceps with
vs barbell, trunk
CON extension, squat,
(21.710.1 supine bench
8) press, knee
n=20 flexion, standing
(total) shoulder press,
dead lift, sitting
paddle lift with
device
Ghanbari- F All UT: 40%-1RM 3 circuit 1-min Circuit 9 different LE, LY, NE LE, LY and NE by
Niaki et al. 40%-1RM, 60%-1RM rounds; between exercises: Arm 0-min post in all
2010 n=5 25-s per rounds curl, triceps exercise groups
80%-1RM exercise extension, back
(21.2+1.0)
extension, squat,
vs leg curl, bench
 60%-1RM, Combined% press, overhead
n=5 (40+60+80%- press, dead lift,
(22.2+0.3) 1RM) seated row
vs CON: no
80%-1RM, exercise
n=5
(23.2+0.3)
vs
Combined
%-1RM,
n=5
(24.6+1.7)
vs
CON, n=5
(22.8+1.1)
*Mean
+SEM
Ihalainen M All active: Max: 100%- 15 x 1 3-min Lower Leg press LE, LY, NE, HYP: LE by 0-min
et al. 2014 Max 1RM (Max) (Max) body mixed cells post, then towards
strength, (BA, EO, BL (but remained ).
n=12, MO, LY, NE and mixed
HYP: 80%- 5 x 10 2-min immature
vs 1RM (HYP) (HYP) cells by 0-min post
precursor then to BL by 30-
HYP, n=12 cells) min post
(28.23.5) MAX: LE by 30-
min post
LY and NE by 15-
min post and
remained
Kraemer M All RT: Cortisol 8 x 10 1- Lower Leg press LE, LY, LE in both groups
et al. 1996 groups: 100%- min/3- body MO, BA
10RM min EO, NE
 High CON: no *Cortisol was not
cortisol, exercise related to response
n=9 profiles
vs
Low
cortisol,
n=9
vs
CON, n=9
26.94.8
Mayhew et M All RT: 65%-1RM 10 x 10 1- Lower Leg press LE, LY, All measures by 0-
al. 2005 1-min rest, min/3- body MO, NE min post
n=9 min *Change in LY and
vs MO was greatest in
1-min rest group
3-min rest,
n=9
22.20.3
Miles et al. W UT and 75%-1RM 6 x 10 2-min Full body Squat Gran, LY, All cell types by 0-
2003 RT: MO, min post
Total CD3+CD4+ *No difference
body, n=34 cells, between groups, or
CD3+CD8+ training status
vs cells,
Upper CD16+/56+
body, n=30 cells, CD19+
cells
Mooren et M IRT 75%-1RM 3 circuit 2-min Circuit Eight different LE, LY, NE IRT: LE, LY and NE
al. 2012 vs (IRT) rounds rest exercise: bench by 3-h post;
60%-1RM of 8 between press, latissimus returned to BL by
MRT exercise exercise pulldowns, 24-h post
(MRT)
n=15 s ; 3-min seated rows,
(total) rest shoulder press,
leg press,
 (26.91.0) between shoulder press,
rounds biceps curls, and
leg curls
Natale et M RE, n=8 60-70%-1RM 3 x 10 Not Upper and 5 different LE, LY, RE: LE and LY
al. 2003 vs (RE) provide lower body exercises: biceps MO, NE, post and remained
CON (no d curl, knee CD3+CD4+ at 3-h post
CON, n=8 station, cells,
exercise) *NE and MO
(24.92.3) hamstring curl, CD3+CD8+ accounted for the
*MeanSE bench press and cells, majority of the in
M leg press. CD16+/56+ LE
cells,
CD3+/CD16 CD3+CD8+ cells by
+/56+ cells, 0-min post and to
CD19+ cells BL by 3-h post
CD16+/56+ cells by
0-min post and
returned to BL by 3-
h post
CD19+ cells by 3-h
post

Peake et M All UT: 10%-max 10 x 60 1-min Upper Eccentric LE, LY, LE by 3-h post
al. 2006 Sub-max isometric (sub- rest limb contractions of MO, NE NE by 3-h post
RE, n=10 strength (Sub- max) (sub- eccentric the elbow flexors
max) max) MO - no change
vs 10 x 3
100%-max (max) 3-min
MAX RE, isometric rest LY no change
n=10 strength (max)
(22.94.7) (MAX) 2-s rest
between
reps
(both
groups)
Potteiger W RT, n=6 100%-10RM 3 x 10 3-min Upper and 7 different LE LE at 90-min and
et al. 2001 (22.81.6) lower body exercises: Leg 180-min post (UT
vs press, bench only)
press, leg
UT, n=9 extension,
(22.90.9) overhead press,
*mean seated rows, leg
SEM curls, biceps
curls

Ramel et M RT, n=7 75%-1RM 2 sets 60-s Circuit 10 different NE NE by 0-min post
al. 2004 vs (75% max reps (mean 9 exercises: bench (RT/UT)
for crunch) reps) press, leg press,
UT, n=10 latissimus dorsi
(29.57.1) pull, leg
extension,
shoulder press,
triceps exercise,
crunch, vertical
row, biceps curl,
pull-up.
Ramel et M RT, n=7 75%-1RM 2 sets 60-s Circuit 10 different LE, LY, All cell types by 0-
al. 2003 vs (75% max reps *mean exercises: bench MO, NE, min post.
for crunch) 11 reps press, leg press, CD3+CD4+ *CD16+/56+ cells
UT (but latissimus dorsi cells,
END for RT; approx. 250% then
8 reps pull, leg CD3+CD8+ below BL by 30-min
active), extension, cells,
n=10 for UT post
shoulder press, CD16+/56+
(29.57.1) triceps exercise, cells *CD3+CD4+
crunch, vertical approx. 20%
 row, biceps curl, *CD3+CD8+ then
pull-up. below BL by 30-min
post
*NE and MO
remained and
peaked at 2-h post
(final time-point)

Simonson M All UT: UT: 75%-1RM 3 x 8-10 1:2 Circuit 8 different LE, LY, RE:
and RE, n=8 CON: no W:R exercises: MO, BA, MO/NE/LY by 0-
Jackson exercise ratio Abdominal EO, NE, NK min post, then began
2004 vs crunches, chest cells, CD4+ to
CON, n=8 press, latissimus cells, CD8+
dorsi pull-downs, cells. NK cells, CD8+ and
(307) CD4+ cells by 0-
leg curls, leg
extensions, leg min post; CD8+ cells
press, seated to BL by 15-min
rows, shoulder post
press. NK cells and CD4+
cells to BL by 30-
min post.
Only NE did not =
BL by 30-min post.
Szlezak et M RT, n=9 RT/UT: 4 x 60-s 60-s Upper Thumb exertion: CD3+CD4+ UT: CD3+CD4+,
al. 2016 (285) 2 x 50%-MVC; limb: lateral pinch cells, CD3+CD8+ and
vs 2 x 35%-MVC Isometric CD3+CD8+ CD19+ cells by 20-
cells, CD19+ min post, then to
UT, n=9 PLA: cells, BL by 60-min post
(277) No exercise CD16+/56+ RT: delayed by 60-
vs cells min post
RT PLA,
n=9 (277)
 Szlezak et M RT, n=10 RT/UT: 4 x 60-s 60-s Upper Thumb exertion: LE, LY, LE and LY by 0-
al. 2015 (275) 2 x 50%-MVC; limb: lateral pinch MO, BA, min post.
vs 2 x 35%-MVC Isometric EO, NE, MO by 60-min post
UT, n=10 PLA: No (RT/UT)
(277) exercise
vs
RT PLA,
n=10
(267)

Abbreviations: BA = basophils; EO = eosinophils; Gran = total granulocytes; LE = total leukocytes; LY = total lymphocytes; MO = monocytes; NE
= neutrophils

CON = control; PLA = placebo F = female; M = male UT = untrained; RT = resistance trained BL = baseline; HYP = hypertrophy; MVC =
maximum voluntary contraction; Post = post-exercise; RE = resistance-exercise; RM = repetition maximum; W:R = work : rest ratio IRT =
intensive resistance test; MRT = moderate resistance test