Edited by: Pantelis Theodoros Nikolaidis, University of West Attica, Greece
Reviewed by: Heidemarie Haller, Knappschafts Hospital, Germany; Sidney B. Peres, State University of Maringá, Brazil
This article was submitted to Exercise Physiology, a section of the journal Frontiers in Physiology
†ORCID: Ciro Alexandre Mercês Gonçalves
Ísis Kelly dos Santos
Matheus Dantas
Ricardo Oliveira Guerra
Geraldo Barroso Cavalcanti Júnior
This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
The immune system (IS) is a complex interaction between cells and molecules that acts to protect the host against possible microorganism invasions, prevent disease and enable wound healing (Simpson et al.,
Interestingly, physical exercise has been shown to be a stressor capable of promoting an acute breakdown of the IS stable state and promoting chronic adaptations (Córdova et al.,
Several immunological markers change after long periods of physical exertion allowing the “open window” phenomenon to occur for 3 to 72 h which decreases immunity and provides a greater onset of airway infections (Pedersen and Ullum,
Despite the existence of evidence on the effects of physical exercise on the immune system of trained individuals, cyclists, triathletes and marathon runners, the acute and chronic responses brought on by aerobic exercise need to be investigated due to the existence of omissions related to the recommendations that stimulate changes in the immunological markers (Nieman et al.,
This systematic review was performed following the guidelines and recommendations of the PRISMA Systematic Review and Meta-Analysis Preferred Report items (Moher et al.,
The studies were searched for in the following databases: MEDLINE (via PubMed), Science Direct, Scopus, Web of Science, SciELO, Bireme and Cochrane Library. The following search strategies, terms (MESH), and Boolean operators were considered: “physical activity” OR exercise OR training AND “Immune System” OR “immune function” OR “immune cell” AND “killer cell” OR “t cell” OR “cytokine*” OR “interleukin*” OR “leukocyte*” OR “lymphocyte*” OR “adhesion molecule” AND “adult*” OR “human*”. The last search was performed in March 2019. Two authors (CAMG, IKS) independently reviewed the titles and abstracts (Level 1). Subsequently, full versions of the articles that met the inclusion criteria were obtained (Level 2). After the analyzes, the reference list of the articles that met the criteria was analyzed to identify additional studies. The study analyzes were resolved with the help of a third author (MPD), duplicate studies with lack of content and access (after sending an email to the authors requesting more information) were excluded.
Inclusion criteria were as follows: randomized controlled trials (RCTs) and non-randomized controlled trials (NRCTs), interventions that use acute or chronic aerobic exercise, which analyze certain markers of the immune system, and healthy adults of both sexes aged between 20 and 45 years. This age group excluded adolescent individuals and menopausal women due to immunological interference (Giefing-Kröll et al.,
Outcome measurements assessed to understand the involvement of cells, immune cells and binding molecules in short and long term exercise were: Leukocytes, neutrophils and granulocytes; NK and NKT Lymphocytes and Cells: CD3+, CD4+, CD8+, CD16+, CD18+, CD19+, CD20+, CD22+, CD44+, CD45+, CD56+, CD95+, and their proportions; Cytokines and interleukins (IL): IL-1, IL-2, IL-6, IL-8, IL-10, and IL12; Tumor Necrosis Factor (TNF-α); Interferon-Gamma (IFN-γ); Immunoglobulin (Ig): IgG, IgA, and IgM; Adhesion Molecules: ICAM-1, ICAM-2, ICAM-3 (Pedersen and Hoffman-Goetz,
The quality and risk of bias assessment of each included study was independently assessed by three authors (CAMG, MPD, IKS) using the Cochrane Risk of Bias Tool (Higgins and Green,
Initially, 8,633 articles were selected from the databases. After analysis, 2,708 articles were excluded because they were duplicated. 5,707 studies were then excluded by the analysis of titles and abstracts. Of the total, 218 studies had their full texts analyzed, and 203 were excluded because they were not eligible according to the inclusion criteria (
Summary of search result.
The characteristics of the selected studies are shown in
Characteristics of the studies.
Akerstrom et al. ( |
Non-RCTs |
11 | Men Health |
Same as experimental | Cycling | – | 120 | – | 60% |
Edwards et al. ( |
Non-RCTs |
24 | 12 Men |
Same as experimental | Cycle ergometer | – | 45 | – | Exercise 1: (M) 130 W (W) 95 W ↑ 35 W−3' (exhaustion) |
Gabriel and Kindermann ( |
Non-RCTs |
13 | Men Health |
Same as experimental | Cycle ergometer | – | To exhaustion | – | 110% |
Gannon et al. ( |
Non-RCTs |
10 | Men Health |
Same as experimental | Cycle ergometer | – | 120 | – | 65% |
Green et al. ( |
RCT |
12 | Men Runners |
Same as experimental | Treadmill racing | – | 60 | – | 95% |
Kurokawa et al. ( |
Non-RCTs |
8 | Men Health |
Same as experimental | Cycle ergometer | – | 60 | – | 60% |
LaPerriere et al. ( |
RCT |
14 | 7 Men Health |
7 Men |
Cycle ergometer | 10 | 45 | 3 | 70–80% |
Li and Cheng ( |
Non-RCTs |
10 | Men Health |
Same as experimental | Cycle ergometer | – | 120 | – | 55% |
Mitchell et al. ( |
RCT |
21 | 11 Men Health Sedentary |
10 Men Health Sedentary |
Cycle ergometer | 12 | 30 | 3 | 75% |
Moyna et al. ( |
RCT |
64 | 32 Adults Health |
32 Adults Health |
Cycle ergometer | – | 18 | – | 55/70/85% |
Moyna et al. ( |
RCT |
64 | 32 Adults Health |
32 Adults Health |
Cycle ergometer | – | 18 | – | 55/70/85% |
Nehlsen-Cannarella et al. ( |
RCT |
12 | Women Health |
Same as experimental | Treadmill walking | – | 45 | – | 60% |
Nehlsen-Cannarella et al. ( |
RCT |
12 | Women Health |
Same as experimental | Track walking | – | 45 | – | 60% |
Ronsen et al. ( |
RCT |
9 | Men Athletes |
Same as experimental | Cycle ergometer | – | 75 | – | 75% |
Scharhag et al. ( |
Non-RCTs |
12 | Men Athletes |
Same as experimental | Cycling on the running track | – | 240 | – | 70% |
The total of participants in the studies were 296 healthy individuals, 196 men and 100 women. Ten studies only included men (including studies with chronic effects), 3 studies investigated men and women and just 2 studies in the included sample were women only. In the studies selected in this review, the samples were composed of triathletes and runners (Gabriel and Kindermann,
Acute intervention was used in most studies included in this systematic review. The interventions performed in these observations were: cycling (Akerstrom et al.,
Prescription intensity was presented as heterogeneous, using as a parameter the percentage of VO2max, which ranged between 60, 65, and 75% (Nehlsen-Cannarella et al.,
To estimate workload, the intensity percentage was multiplied by the time in minutes of the intervention. Among the studies that used VO2max, Gannon et al. (
In the 13 acute studies, 12 had the duration in their interventions range from 18 to 240 min and 1 study went to exhaustion. In chronic studies, however, different prescription parameters were set, but these can be considered moderate intensities. Regarding the duration of interventions, the data were heterogeneous, since one study lasted 10 weeks with 45-min sessions (1,350 min of exercise; LaPerriere et al.,
The effect of post-aerobic regulation on the immunological markers that were evaluated in the studies are shown in
Post-aerobic exercise regulation and immunological markers.
Akerstrom et al. ( |
↔ | ||||||||||||||||||||||
Edwards et al. ( |
↑ | ||||||||||||||||||||||
Gabriel and Kindermann ( |
↑ | ||||||||||||||||||||||
Gannon et al. ( |
↑ | ↑ | ↓ | ↑ | ↔ | ||||||||||||||||||
Green et al. ( |
↑ | ↑ | ↑ | ↑ | |||||||||||||||||||
Kurokawa et al. ( |
↑ | ↑ | ↑ | ↔ | ↔ | ↑ | |||||||||||||||||
LaPerriere et al. ( |
↔ | ↔ | ↔ | ↑ | ↑ | ↔ | ↔ | ↑ | |||||||||||||||
Li and Cheng ( |
↑ | ↑ | ↑ | ↑ | |||||||||||||||||||
Mitchell et al. ( |
↔ | ↔ | ↔ | ↔ | |||||||||||||||||||
Moyna et al. ( |
↑ | ↑ | ↓ | ↑ | ↓ | ||||||||||||||||||
Moyna et al. ( |
↑ | ↑ | ↑ | ↑ | ↑ | ↑ | ↑ | ↑ | ↓ | ↑ | ↑ | ||||||||||||
Nehlsen-Cannarella et al. ( |
↑ | ↑ | ↔ | ↑ | ↔ | ↔ | |||||||||||||||||
Nehlsen-Cannarella et al. ( |
↑ | ↑ | ↔ | ↑ | ↔ | ↔ | ↑ | ↑ | ↔ | ||||||||||||||
Ronsen et al. ( |
↔ | ↑ | |||||||||||||||||||||
Scharhag et al. ( |
↑ | ↑ | ↑ | ↔ | ↔ | ↑ | ↑ |
In the lymphocyte subpopulations of the immune system there are contradictory results. Two studies investigated the effect of acute exercise on CD3+ T cells, showing an increase in the count of these cells (Moyna et al.,
Few studies from those included in this review addressed the effect of aerobic exercise on interleukins. Exercise has not been found to promote IL-1 alteration (Ronsen et al.,
After using the Cochrane risk of bias tool, the results are shown in
Random sequence generation: In 11 studies no process methods were described for the generation of their random sequences, characterized as risk of unknown bias. These methods could be by generating random computer numbers, throwing coins, shuffling cards or envelopes, throwing dice or by lottery.
Allocation concealment: 12 articles in their entirety did not provide sufficient information, so, in this way, it was not possible to detect how the sequence and allocation of participants occurred.
Blindness of practitioners, participants, outcome assessors: In randomized controlled trials using exercise intervention, everyone involved cannot be blinded to treatment allocation. In the studies where supervised physical exercise was administered, the professionals who performed the intervention could not be blinded. Regarding the blindness of the outcome evaluators, this information did not exist in the evaluated studies. These facts meant that the classification of all the studies had an “unclear” risk of bias, i.e., unknown because of their lack of information.
Incomplete outcomes: In 13 studies, it was impossible to verify risk bias for losses and for the sampling stages due to the lack of described information related to randomized numbers and the reasons for losses.
Selective outcome: It can be observed that in all the studies the risk of bias for reporting a selective outcome was classified as unknown due to insufficient information in the studies. They did not have their protocols or did not allow access to them.
Other sources of bias: These sources were easily detected in 10 studies. In these there was no information relating to the nutritional status of the participants during data collection or any daily dietary report in the weeks prior to these same study evaluations.
The present systematic review aimed to analyze the scientific evidence on the acute and chronic effects of aerobic exercise on immune markers in healthy individuals. It was found in our study that aerobic exercise promotes changes in the immune response of leukocytes, lymphocytes, lymphocyte subpopulations, interleukins, NK cells and immunoglobulins. Several authors confirm the occurrence of these modifications in the same immunological markers due to the performance of cardiorespiratory physical training (Barron et al.,
A large number of studies analyze the likely effects of aerobic exercise on immune cells by bringing together individuals of both genders in their samples (Morgado et al.,
Several authors report acute and chronic changes in immune system cells in practitioners of aerobic sports such as running, cycling, triathlon, and skating (Díaz et al.,
Aspects related to the studies analyzed, such as the participants' level of physical fitness, type of intervention, in regard to its time and intensity, and the use of contraceptives by women may interfere with the analyzed immune cell concentrations. These possible changes in immune function bring up an important question to be answered through further investigation in future studies.
Acute aerobic exercise has been shown to be a potential influencer of immune cell concentrations, while data from chronic studies are still contradictory (Mitchell et al.,
In many studies, authors report that acute aerobic exercise promotes changes in most immune markers like leukocytes, lymphocytes, and natural killer cells, among others (Scharhag et al.,
Mid-distance running (21.1 km) stimulates growth in leukocyte, neutrophil and monocyte numbers in amateur runners (Lippi et al.,
Lymphocyte subpopulations also increase with 10-week aerobic training, with three sessions of 45 min per week on the cycle ergometer at 70–80% intensity of the predicted maximum heart rate per age (LaPerriere et al.,
As a limitation of this study, we can highlight the difficulty of finding studies with experimental and controlled conditions. Regarding the physical fitness of the chosen study participants, which can vary from sedentary to athlete, the results cannot be generalized. In regard to gender, which is a factor of great influence on the immune system, only five articles were found from all the articles selected that investigated the female sex and in three of these both of the sexes were mixed in the sample. In regard to the intensity of physical effort used in the interventions, there is the limitation of stipulating a zone of training when considering the heterogeneity found, and that each one has an acute or chronic effect on a certain immunological marker. Another limitation of our study was the difficulty of finding studies that report on the chronic effect of exercise with only two studies being chosen for this review, thus not allowing a thorough analysis of this aspect.
In addition, the use of birth control pills in studies with women limits our ability to reach conclusions. Thus, there is a considerable need for further studies in order to identify the factors that really influence these discrepancies and also further research is needed in chronic intervention to verify its actual interference with immunological markers.
We therefore highlight the exclusivity of this review because it is the first to widely cover this subject analyzing the effects of acute and chronic aerobic exercises on all existing immunological markers. The inclusion of randomized studies, the methodological precautions adopted to reduce the risk of bias, the predefinitions of a protocol to be registered on a specific web platform, and the inclusion of experimental studies with control and experimental groups of similar characteristics helped in the observation of the true interference of aerobic exercise on immune cells. These facts show that this study has made an important contribution with great research potential within the existing scientific literature.
According to the results found in this research it was possible to understand which immune markers are affected by aerobic exercise from acute and chronic perspectives. Aspects such as the intensity of each intervention performed, its type, the place where it was developed and the characteristics of the individuals undergoing it make up important knowledge that allows for a better understanding of these immunological changes caused by aerobic exercises. This review provides an up-to-date insight into the content investigated herein, improving the safety in the work of health professionals when prescribing these aerobic exercises for healthy adults in the promotion of health.
Therefore, it is concluded from the results found in this study that acute intervention promotes changes in most immunological markers while chronic interventions influence a smaller part of them. There were differences between the results of studies with acute intervention with certain immunological markers. These may be related to the level of physical fitness of the subjects, and type and intensity of intervention.
External factors such as characteristics of the environment where the intervention was performed and its intensity and also the internal aspects related to the training time and oral contraceptive use of the participants should be taken into consideration in new studies for a better understanding of the relationship between aerobic exercise, acute and chronic interventions and their real influence on immunological markers.
CG, MD, and IS contributed to the conception and design, search, and eligibility and outcome measures. CG, MD, and GJ contributed to the quality assessment. CG, MD, IS, PD, DS, and GJ contributed to the writing of the manuscript. CG, MD, IS, PD, DS, BC, RG, and GJ contributed to the revision and approval of the final manuscript version and interpretation of the results.
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
The Supplementary Material for this article can be found online at: