Exercise Immunology Review, an official publication of the International Society of Exercise and Immunology and of the German Society of Sports Medicine and Prevention, is committed to developing and enriching knowledge in all aspects of immunology that relate to sport, exercise, and regular physical activity. In recognition of the broad range of disciplines that contribute to the understanding of immune function, the journal has adopted an interdisciplinary focus. This allows dissemination of research findings from such disciplines as exercise science, medicine, immunology, physiology, behavioral science, endocrinology, pharmacology, and psychology. Exercise Immunology Review publishes review articles that explore: (a) fundamental aspects of immune function and regulation during exercise. (b) interactions of exercise and immunology in the optimization of health and protection against acute infections. (c) deterioration of immune function resulting from competitive stress and overtraining. (d) prevention or modulation of the effects of aging or disease (including HIV infection; cancer; autoimmune, metabolic or transplantation associated disorders) through exercise. (e) instrumental use of exercise or related stress models for basic or applied research in any field of physiology, pathophysiology or medicine with relations to immune function.
International Society of Exercise and Immunology (ISEI)
Immunometabolic profiling of T cells in response to prolonged moderate intensity cycling in humans
Background: Emerging data indicates that enrichment of peripheral blood with T lymphocytes during exercise and their associated changes in function are underpinned by modulation of cellular bioenergetics. However, there is a dearth of literature examining these responses using metabolic thresholds to prescribe exercise intensity or providing single cell resolution on immunometabolic outcome measures. Objectives: The current study was designed to examine the metabolic phenotypes and real-time bioenergetic responses to activation of enriched naive helper (CD4(+)) and cytotoxic (CD8(+)) T cells and peripheral blood mononuclear cells (PBMCs) in response to prolonged cycling. Methods: Ten aerobically trained males and females (mean +/- SD: age 21 +/- 1 years; maximal oxygen consumption: 53.9 +/- 9.8 ml . kg(-1) . min(-1)) undertook a 2-hour bout of continuous cycling at a power output eliciting 95% lactate threshold-1. Blood samples were collected at rest, immediately (post), and 2 hours after cycling cessation (recovery). Using injection sequences of cell respiration modulators and a CD3/CD28 activator, bioenergetic profiles of PBMCs and enriched naive CD4(+) and CD8(+) T cells were determined using extracellular flux analysis. Mitochondrial membrane potential (Delta Psi m) was examined using flow cytometry. Results: Despite cycling evoking significant fluctuations in peripheral blood T cell numbers, there were no changes in absolute or relative measures of mitochondrial respiration, glycolytic flux and ATP synthesis rate post and recovery vs rest. Contribution of mitochondrial respiration to ATP production was greater than glycolysis in naive T cells across all timepoints, but not PBMCs in recovery. This was despite absolute and relative changes in Delta Psi m of memory T cells being greater in recovery vs. rest. Bioenergetic responses to ex vivo T cell activation were not different between cell types or timepoints. Conclusion: These data indicate that the metabolic phenotypes of naive T cells and PBMCs were largely unaltered within 2 hours of prolonged moderate intensity cycling.
Copyright (c) 2025 Exercise Immunology Review https://rightsstatements.org/page/InC/1.0/
Exercise-Induced Metabolic Reprogramming and Immune Modulation: A Novel Strategy for Cancer Therapy
Exercise represents a non-pharmacological strategy capable of concurrently modulating tumor metabolism and immunity. Regular physical activity reprograms systemic and tumor-localized metabolic networks, including glucose, lactate, amino acid, and lipid pathways, while enhancing innate and adaptive immune responses. Exercise-induced myokines (e.g., IL-6, IL-15, irisin, SPARC) and improved vascularization contribute to reshaping the tumor microenvironment (TME), mitigating immunosuppressive metabolite accumulation, and promoting T cell and NK cell infiltration. Mechanistically, exercise activates integrated signaling networks including AMPK-mTOR-HIF1 alpha, PGC-1 alpha-ERR alpha, and IL-6/STAT3 axes, supporting metabolic flexibility and anti-tumor immunity. Translational and clinical studies suggest exercise can enhance chemotherapy and immunotherapy efficacy, while precision exercise prescriptions based on FITT principles, biomarkers, and patient-specific tolerance may maximize therapeutic benefits. This review summarizes the molecular and systemic mechanisms of exercise-induced metabolic-immune reprogramming and outlines strategies for clinical translation in oncology.
Less Inflammatory Debris, Improved Immunity from Immune Detox: A New Perspective on the Benefits of Exercise in Chronic Disease
The immunological benefits of exercise are commonly attributed to its immune-boosting effects such as the release of exercise-induced factors (e.g., exerkines) and activation of anti-inflammatory molecules. However, this may not fully explain its benefits in chronic inflammatory conditions. We propose a complementary view whereby exercise potentially functions as a biological detoxifier by removing harmful immunological debris such as damage-associated molecular patterns (DAMPs), senescent cells, dysfunctional mitochondria and pro-inflammatory extracellular vesicles (EVs) that drive chronic immune activation. We highlight key mechanisms by which exercise may reduce or remove these harmful signals, including autophagy and mitophagy activation, enhanced efferocytosis, reduced senescence burden, and modulation of EV cargo. This ""immune detox"" model may help explain the clinical benefits of exercise in conditions where the immune system is overactivated, not deficient. It shifts the narrative from immune boosting to restoring immune balance, and could have potentially important implications for biomarker discovery and personalized exercise prescriptions in chronic disease.
Occurrence of acute respiratory illnesses in athletes: a systematic review and meta-analysis
Background: Estimating the occurrence of acute respiratory illness (ARI) in athletes is crucial for understanding the need for preventive measures. This study aimed to estimate the occurrence of ARIs in athletes compared to non-athlete controls. We evaluated which of the published studies on the occurrence of ARI in athletes were eligible, giving due consideration to the epidemic nature of viral ARIs. Methods: We performed a systematic search of PubMed, EBSCOhost, and Web of Science databases from January 1990 to May 2023. Only studies reporting the occurrence of ARIs in athletes, with a duration of at least 12 months and simultaneously employing non-athlete controls, were included. The random effects model was used to calculate the incidence rate ratio (IRR) of ARI in athletes compared to non-athlete controls, with 95% confidence intervals. Results: Our search yielded 218 results, of which 6 studies met the essential criteria for viral ARIs and were included in our metaanalysis. Since the exact number of ARIs was not reported in many studies, we had to estimate the total number of ARIs for both athletes and non-athlete controls. The occurrence of ARIs was 1.87 times higher in athletes compared to non-athlete controls (3.2 vs 1.7, pooled IRR 1.87, 95% CI 1.08 to 3.26). Publication bias analysis or a funnel plot was not evaluated because the primary objective of none of the studies was to determine the occurrence of ARI in athletes. Most of the studies on the occurrence of ARIs in athletes had a duration of less than 12 months and did not include a concurrent control group, making them ineligible considering the seasonal and contagious nature of ARIs. Conclusion: Our meta-analysis suggests that athletes suffer from significantly more ARIs than non-athletic subjects. Our observations highlighted the lack of high-quality long-term studies on the occurrence of ARIs in athletes.
Is stretching an appropriate control for studies on exercise immunology in older adults? A systematic review
Objective: Active muscle contraction is assumed to be essential in the anti-inflammatory effect of physical exercise, also in older adults. Although stretching does not involve active muscle contractions, its (anti)inflammatory effects remain unclear. This systematic review aims to determine whether stretching affects the inflammatory profile of older adults and if it can be considered as an appropriate control intervention for exercise immunology studies. Methods: This systematic review was registered in PROSPERO (CRD42023388920) and conducted in accordance with PRISMA guidelines. PubMed and Web of Science were systematically screened for articles describing the effect of muscle stretching on the inflammatory profile (immune cell proportions, cytokines, oxidative markers, and inflammatory gene expression in muscle/immune cells) in older adults. A methodological quality assessment was performed using the ROB2 tool and effect sizes (ES) were calculated. Results: Nine randomized controlled trials were included, all showing sufficient methodological quality and reporting effects on basal levels of inflammation. Muscle stretching had no effect on the number of na & iuml;ve, memory, and senescence-prone T-cells or circulating inflammatory markers CRP and IL-6 neither on most studied oxidative stress markers (SOD, NO, VCAM, ICAM, PTX3, OX-LDL, MDA, HNE, nitrotyrosine, ox-LDL, and protein carbonyls). However, the oxidative stress marker LPO increased (ES=0.76) while CAT, ROS, fibrinogen, andMDA-LDL decreased (ES between-0.50 and-0.63) after stretching in older persons with chronic diseases. Contradictory results were found for TNF-alpha and gene expression levels. One study observed no changes in circulating TNF-alpha after stretching in healthy women, while another study showed an increase in muscle gene expression of TNF-alpha (ES=1.60) as well as circulating TNF-alpha (ES=0.64) in men with peripheral arterial disease. Regarding gene expression changes in pro/anti-inflammatory related genes, one study analysing RNA extracted from peripheral blood mononuclear cells showed stretching-induced increases (fold change >= 1.5) or decreases (fold change <= 0.67), while another study using RNA from buffy coat samples demonstrated no effect on gene expression. Conclusion: Passive or active types of muscle stretching appears to be a suitable active control for exercise immunology studies in older populations. However, in populations with peripheral artery disease stretching may affect the inflammatory profile, possibly due to a higher overall inflammatory status.
Unleashing anti-tumour immunity: dietary restriction and exercise interventions adjunct to chemotherapy for cancer patients
Conventional chemotherapies can stimulate the immune system by increasing tumour antigenicity (e.g., neoantigen exposure to immune cells) and altering adjuvanticity in the tumour (e.g., danger associated molecular patterns and cytokines). These molecules promote the recruitment, activation, and maturation of dendritic cells, which in turn, prime and activate cytotoxic T cells against tumour cells. However, several factors can decrease the immunostimulatory efficacy of chemotherapeutic agents. These include reduced tumour cell antigenicity and adjuvanticity and compromised immune function at a local and systemic level. Findings from preclinical studies show that dietary restriction and exercise promote systemic changes that may help to restore immune system function through several mechanisms, including an enhanced infiltration and function of antitumoral immune cells and a decrease in immunosuppressive cells, leading to a reduction in tumour volume. In addition, dietary restriction and exercise training in mice have been shown to enhance the efficacy of chemotherapy. In human studies there is also emerging evidence that dietary restriction and exercise can impact the immune system towards a more antitumoral profile. In this review, we discuss the immunostimulatory effects of dietary restriction (caloric restriction and fasting) and exercise training in preclinical cancer models, and potential synergies with chemotherapy. We then review clinical studies assessing the effects of these interventions on immune-related endpoints and tumour responses. Finally, we propose that combining dietary restriction with exercise could be a promising strategy to increase chemotherapy efficacy.
Copyright (c) 2024 Exercise Immunology Review https://rightsstatements.org/page/InC/1.0/
Involvement of neutrophils and macrophages in exhaustive exercise-induced liver, kidney, heart, and lung injuries
Moderate exercise is effective for maintaining or improving overall health. However, excessive exercise that exhausts the adaptive reserve of the body or its ability to positively respond to training stimuli can induce tissue damage and dysfunction of multiple organs and systems. Tissue injury, inflammation, and oxidative stress are reportedly induced the skeletal muscles, liver, and kidneys after exercise. However, the precise mechanisms underlying acute tissue injury after intense exercise have not yet been fully elucidated. Studies using various experimental models of acute tissue injury, other than intense exercise, have demonstrated infiltration of inflammatory cells, including neutrophils and macrophages. These cells infiltrate injured tissues and induce inflammatory and oxidative stress responses by producing inflammatory cytokines and reactive oxygen species, thereby exacerbating tissue injury. In addition to the activation of blood neutrophils and increase in their levels during and/or after prolonged or intense exercise, chemokines that contribute to leukocyte migration are released, facilitating the migration of neutrophils and monocytes into tissues. Therefore, neutrophils and macrophages, activated by exhaustive exercise, may infiltrate tissues and contribute exhaustive exercise-induced tissue injury. Recently, the contributions of neutrophils and macrophages to various tissue injuries caused by exhaustive exercise have been reported. In this review, we summarize the involvement of neutrophils and monocytes/macrophages in exhaustive exercise-induced non-skeletal muscle tissue injury. In addition, we present novel data demonstrating the contribution of neutrophils and macrophages to exhaustive exercise-induced cardiac and pulmonary injuries. Our study findings and the evidence presented in this review suggest that neutrophils and macrophages may play pivotal roles in exhaustive exercise-induced tissue injuries.
Immune Response to COVID-19 Vaccination in Elite Athletes
Purpose: This study analyses the immune response of elite athletes after COVID-19 vaccination with double-dose mRNA and a single-dose vector vaccine. Methods: Immunoglobulin G (IgG) antibody titers, neutralizing activity, CD4 and CD8 T-cells were examined in blood samples from 72 athletes before and after vaccination against COVID-19 (56 mRNA (BNT162b2 / mRNA-1273), 16 vector (Ad26.COV.2) vaccines). Side effects and training time loss was also recorded. Results: Induction of IgG antibodies (mRNA: 5702 BAU/ml; 4343 BAU/ml (hereafter: median), vector: 61 BAU/ml; 52 BAU/ ml, p<0.01), their neutralizing activity (99.7%; 10.6%, p<0.01), and SARS-CoV-2 spike-specific CD4 T-cells (0.13%; 0.05%; p<0.01) after mRNA double-dose vaccines was significantly more pronounced than after a single-dose vector vaccine. SARS-CoV-2 spike-specific CD8 T-cell levels after a vector vaccine (0.15%) were significantly higher than after mRNA vaccines (0.02%; p<0.01). When athletes who had initially received the vector vaccine were boostered with an mRNA vaccine, IgG antibodies (to 3456 BAU/ml; p<0.01), neutralizing activity (to 100%; p<0.01), CD4 (to 0.13%; p<0.01) and CD8 T-cells (to 0.43%; p<0.01) significantly increased. When compared with dual-dose mRNA regimen, IgG antibody response was lower (p<0.01), the neutralizing activity (p<0.01) and CD8 T-cell (p<0.01) response higher and no significant difference in CD4 T-cell response (p=0.54) between the two regimens. Cumulative training loss (3 days) did not significantly differ between vaccination regimens (p=0.46). Conclusion: mRNA and vector vaccines against SARS-CoV-2 appear to induce different patterns of immune response in athletes. Lower immune induction after a single-shot vector vaccine was clearly optimized by a heterologous booster. Vaccine reactions were mild and short-lived.
Investigating the impact of exercise on T and NK cells in skin cancer: a systematic review
Skin cancer has the highest incidence of all cancers, and their incidence are increasing in both melanoma and non-melanoma skin cancers. Alternative adjuvant treatment strategies appropriate for their management are needed. Modifiable lifestyle factors influence disease outcomes, either improving or worsening outcomes. Exercise is an example of a modifiable lifestyle factor, and can be prescribed as an adjuvant therapy in other cancer types to improve immune function and overall clinical outcomes. The initial aim of the review was to investigate the T-cell specific mechanisms of exercise which affect clinical/disease outcomes in skin cancer. Study quality was assessed by a modified Covidence quality assessment template with animal-model study specific criteria. A total of 10 articles were included; all articles were murine model studies investigating melanoma. Eight studies (n=8) employed a randomised controlled trial design, with two bio-informatics studies, and one study using human data which could solidify a link to human health. While the review focussed initially on T-cells, many studies reported significant changes in NK cells, and as they share the same haematopoietic lineage/ common lymphoid progenitor as T cells, the data was included in the analyses. Most studies indicated that exercise reduced melanoma tumour burden. Exercising prior to melanoma inoculation was most effective for delaying carcinogenesis and reducing tumour burden. Synergism was a topic identified in studies; PD-1/PD-L1 treatment, and exercise were not synergistic. Conversely, exercise and mental stimulation were synergistic, and the temperature at which exercise was conducted significantly reduced tumour burden. Several murine studies reported that exercise improved clinical outcomes in melanoma, and that long-term exercise was more effective in reducing tumour burden. Further studies are required to investigate this relationship in humans, and in other types of skin cancer.
Higher risk of upper respiratory tract infection post marathon running: when physical exercise becomes a threat to the immune system
Background: Several studies have reported that marathon runners have a higher risk of upper respiratory tract infections (URTI) post marathon than non-exercising controls. However, other studies did notfind a higher risk of URTI in the same participants before and after a marathon, precluding a conclusive consensus. Besides the between-subjects effects, another important confounding factor in these results is the different pre and post follow-up time to track URTI. Objectives: Identify by meta-analysis whether a marathon running increases the risk of URTI, adjusting the follow-up time to track URTI. Data sources: We searched for articles using MEDLINE (PubMed), Embase, Scopus, Web of Science, the Cochrane Library, andEBSCOhost, combining the marathon and respiratory infection descriptor synonyms, on 1st December 2022. Eligibility criteria: The PICOS framework included human population, comparison between pre and post marathon running, of URTI symptoms (assessed from one to 4 weeks), in non-controlled intervention studies. Data Synthesis: Because follow-up was longer before the marathon in many studies, we adjusted the number of subjects with infections before marathon to the equivalent post-marathon follow-up duration. There was 18% higher incidence of URTI post-marathon (OR 1.18 95%CI [1.05-1.33], p= 0.005) in a very consistent meta-analysis (I2 = 0%, p = 0.69), with no risk of publication bias (Egger test p-value = 0.82) for the 7 studies included. The main issues in the quality of the studies were bias in measuring the outcome, bias in classification of intervention (participation in the marathon) and time-varying confounding (corrected for analysis), and therefore the quality of evidence was moderate (GRADE approach = 3). Limitations: The need for follow-up time adjustment is a limitation, since the number of URTI recorded could be different if the original studies had used the same follow-up time pre and post marathon. The subjectivity of the URTI self-assessments is another limitation in this field. Conclusions: There is an increased risk of URTI post marathon running and research on this topic to understand mechanisms might support runners to find efficient interventions to reduce this risk. Protocol registration on in the International Prospective Register of Systematic Reviews (PROSPERO): CRD42022380991
Combined exercise intervention in a mouse model of high-risk neuroblastoma: effects on physical, immune, tumor and clinical outcomes.
Background: Exercise might exert anti-tumoral effects in adult cancers but this question remains open in pediatric tumors, which frequently show a different biology compared to adult malignancies. We studied the effects of an exercise intervention on physical function, immune variables and tumoral response in a preclinical model of a highly aggressive pediatric cancer, high-risk neuroblastoma (HR-NB). Methods: 6-8-week-old male mice with orthotopically-induced HR-NB were assigned to a control (N=13) or exercise (5-week combined [aerobic+resistance]) group (N=17). Outcomes included physical function (cardiorespiratory fitness [CRF] and muscle strength), as well as related muscle molecular indicators, blood and tumor immune cell and molecular variables, tumor progression, clinical severity, and survival. Results: Exercise attenuated CRF decline (p=0.029 for the group-by-time interaction effect), which was accompanied by higher muscle levels of oxidative capacity (citrate synthase and respiratory chain complexes III, IV and V) and an indicator of antioxidant defense (glutathione reductase) in the intervention arm (all p <= 0.001), as well as by higher levels of apoptosis (caspase-3, p=0.029) and angiogenesis (vascular endothelial growth factor receptor-2, p=0.012). The proportion of 'hot-like' (i.e., with viable immune infiltrates in flow cytometry analyses) tumors tended to be higher (p=0.0789) in the exercise group (76.9%, vs. 33.3% in control mice). Exercise also promoted greater total immune (p=0.045) and myeloid cell (p=0.049) infiltration within the 'hot' tumors, with a higher proportion of two myeloid cell subsets (CD11C+ [dendritic] cells [p=0.049] and M2-like tumor-associated macrophages [p=0.028]), yet with no significant changes in lymphoid infiltrates or in circulating immune cells or chemokines/cytokines. No training effect was found either for muscle strength or anabolic status, cancer progression (tumor weight and metastasis, tumor microenvironment), clinical severity, or survival. Conclusions: Combined exercise appears as an effective strategy for attenuating physical function decline in a mouse model of HR-NB, also exerting some potential immune benefits within the tumor, which seem overall different from those previously reported in adult cancers.
Copyright (c) 2023 Exercise Immunology Review https://rightsstatements.org/page/InC/1.0/
Respiratory viral infections - impact on sport and exercise medicine
Respiratory viruses are the most frequent causative agents of disease in humans and thus also in elite athletes. The COVID-19 pandemic has recently emphasized the entire spectrum of respiratory tract infections worldwide. Understanding the basic elements of respiratory viral infections is a fundamental requirement from the perspective of etiological diagnostics, treatment, and prevention strategy planning, as well as resource allocation.
The anti-inflammatory and bioregulatory effects of habitual exercise in high-fat diet-induced obesity involve crown-like structures and MCP-1 in white adipose tissue.
"Macrophage accumulation in the adipose tissue and changes in their inflammatory phenotype is a hallmark of obesity-induced inflammation, notably forming inflammatory structures known as ""crown-like structures (CLS)"". Exercise can be a key strategy to improve inflammation-related complications, but it is crucial to consider that, although exercise generally exerts systemic and local anti-inflammatory effects, this depends on the basal inflammatory status and exercise modality. In this context, the ""bioregulatory effect of exercise"" implies to achieve the reduction or prevention of an excessive inflammatory response and also the preservation or stimulation of the innate response. In the present work, our aim was to evaluate the effect of regular exercise on adipose tissue inflammation in high-fat diet-induced obesity in mice, as reflected by macrophage infiltration and phenotype, and CLS formation, together with a potential role for the chemokine MCP-1 in this process. Results showed that obesity is associated with greater MCP-1 expression (p<0.05), macrophage accumulation (p<0.05), and CLS presence (p<0.001). Regular exercise reduced macrophage accumulation (p<0.05), MCP-1 expression (p<0.01), and CLS presence (p<0.05) in obese mice; while it increased macrophage and CLS presence (p<0.01), MCP-1 expression (p<0.05), and M2 polarization (p<0.05) in lean mice. MCP-1 was associated with the proliferation of CLS, showing the first image demonstrating a potential role of this chemokine in the development of these structures. Altogether, these results confirm, for the first time, the ""bioregulatory effect of exercise"" in the adipose tissue: reducing inflammation in individuals with an elevated inflammatory set point, but stimulating this response of the immune system in healthy individuals."
A Scoping Review on the Effects of Physical Exercise and Fitness on Peripheral Leukocyte Energy Metabolism in Humans
Background: Both acute and chronic exercise have profound effects on systemic metabolism and the immune system. While acute exercise transiently disturbs energy homeostasis and elicits acute inflammation, exercise training improves systemic metabolic capacity, lowers basal inflammation, and reduces infection risk. Accordingly, accumulating evidence indicates links between systemic and immune cell metabolism and suggests that cellular metabolism may be an important way exercise influences immune function. Yet, no reviews have systematically surveyed the literature in this area. Aims: The aims of this scoping review were to collect, summarize, and provide descriptive analysis of literature on the effects of acute exercise, chronic exercise, and physical fitness on peripheral leukocyte energy metabolism of human adults. Methods: Reports were retrieved from the databases Pubmed, Scopus, and Embase and hierarchically filtered for eligibility. Eligible reports were those that implemented acute or chronic exercise interventions, or assessed physical fitness, in relation to the regulation or function of leukocyte energy metabolism in human adults. Data were charted from eligible reports by two independent reviewers, confirmed by conference, and organized for reporting. Results & Conclusion: Results suggest acute exercise can influence the regulation and function of leukocyte metabolism, with some similarities to what has been previously documented in skeletal muscle. Data also evidence that exercise training and/ or physical fitness alters cellular metabolic regulation and function. Improvements in markers of cell respiratory function or mitochondrial regulation were frequently observed following training or with greater fitness. However, notable gaps in the literature remain. These gaps include: the effects of acute exercise and exercise training on leukocyte glycolysis, the effects of resistance and concurrent exercise, and potential differences in the effects of exercise between immune cell types and subsets. Future research is encouraged to fill the latter gaps and further delineate how exercise influences the immune system and can be used to support overall health.
Exercise-induced effects on inflammatory markers and brain-derived neurotrophic factor in patients with knee osteoarthritis. A systematic review with meta-analysis.
Background: In the pathogenesis of knee osteoarthritis (KOA), inflammatory mediators play an important role. However, the precise underlying mechanism by which regular exercise therapy (ET) exert effects on the immune system in KOA patients is unknown. Objectives: The aim of this systematic review was to investigate the basal and acute effects of ET on inflammatory biomarkers and brain derived neurotrophic factor (BDNF) in KOA patients. Methods: PubMed, Web Of Science and PEDro were systematically searched for appropriate studies. If possible, a meta-analysis was performed or an approximation of the effect size (ES) was calculated. Risk of bias was scored using the Cochrane ROB 2.0 or ROBINS-I tools. Results: Twenty-one studies involving 1374 participants were included. Fifteen articles focused on basal exercise effects, four on acute effects, and two on both. Biomarker analysis (n=18) was performed in synovial fluid (n=4) or serum/plasma (n=17). A meta-analysis demonstrated that basal CRP was reduced in KOA patients 6-18 weeks weeks after ET (MD: -0.17;95%CI[-0.31;-0.03]), while IL-6 (MD: 0.21;95%CI[-0.44;0.85]), and TNF-alpha (MD:-0.57;95%CI[-1.47;0.32]), levels did not significantly change. Also, sTNFR1/2 did not change significantly after ET. For other biomarkers, insufficient data were available to perform a meta-analysis. Nevertheless, a low degree evidence was found for a decrease in IL-6 (ES:-0.596 &-0.259 &-0.513), an increase in sTNFR1 (ES:2.325), a decrease sTNFR2 (ES:-0.997) and an increase in BDNF (ES:1.412). Locally, intra-articular IL-10 (ES:9.163) increased, and IL-1 beta (ES:-6.199) and TNF-alpha decreased (ES:-2.322) after ET. An acute exercise session elicited a myokine response (ES IL-6:0.314), and an increase in BDNF (no ES-data). No inflammatory effect (ES CRP:0.052; ES TNF-alpha:-0.019 0.081) following an acute bout of training was found. However, a single bout of exercise elicited a decrease in intra-articular IL-10 (no ES-data). Conclusion: ET can induce circulatory and intra-articular anti-inflammatory effects in patients with KOA. The anti-inflammatory properties have important implications for informing these patients and clinicians about the underlying ET.
Exercise effect on symptom severity, morbidity and mortality in viral infections: a systematic review and meta-analysis.
There is a knowledge gap regarding the consequences of exercise during acute infections in humans and contradictory findings in animal studies, compromising public health advice on the poten-tial benefits of physical activity for immunity. Here, we carried out a meta-analysis of studies of the effects of moderate exercise (ME) and exercise until fatigue (EF) on symptom severity, morbidity and mortality during viral infection in animal models. The sys-tematic review on PubMed, Scopus, Embase, Web of Science, Co-chrane and EBSCOhost (CINAHL and SPORT Discus) identified 8 controlled studies, with 15 subgroups within them. The studies exposed the animals (mice [7 studies] and monkeys [1 study]) to exercise immediately before or after viral inoculation (HSV-1, H1N1 influenza and B.K. virus) with follow-up for 21 days. ME significantly reduced morbidity (OR 0.43 [0.19; 0.98], P = 0.04) with no change for symptom severity (SMD-3.37 [-9.01; 2.28], P = 0.24) or mortality (OR 0.48 [0.08;3.03], P = 0.43). In con-trast, EF gave a trend towards increased symptom severity (SMD 0.96 [-0.06; 1.98], P = 0.07) and mortality (OR 1.47 [0.96;2.28], P =0.08) with no change in morbidity (OR 1.22 [0.60;2.5], P = 0.58). We conclude that in animals moderate exercise during in-fection is advantageous, whilst exercise until fatigue should be avoided. Further research is required to determine if moderate exercise may also be beneficial in humans during infection.
Copyright (c) 2022 Exercise Immunology Review https://rightsstatements.org/page/InC/1.0/
Effect of high intensity interval training and moderate intensity continuous training on lymphoid, myeloid and inflammatory cells in kidney transplant recipients
Kidney transplantations are seen to be a double-edge sword. Transplantations help to partially restore renal function, however there are a number of health-related co-morbidities associated with transplantation. Cardiovascular disease (CVD), malignancy and infections all limit patient and graft survival. Immunosuppressive medications alter innate and adaptive immunity and can result in immune dysfunction. Over suppression of the immune system can result in infections whereas under suppression can result in graft rejection. Exercise is a known therapeutic intervention with many physiological benefits. Its effects on immune function are not well characterised and may include both positive and negative influences depending on the type, intensity, and duration of the exercise bout. High intensity interval training (HIIT) has become more popular due to it resulting in improvements to traditional and inflammatory markers of cardiovascular (CV) risk in clinical and non-clinical populations. Though these improvements are similar to those seen with moderate intensity exercise, HIIT requires a shorter overall time commitment, whilst improvements can also be seen even with a reduced exercise volume. The purpose of this study was to explore the physiological and immunological impact of 8-weeks of HIIT and moderate intensity continuous training (MICT) in kidney transplant recipients (KTRs). In addition, the natural variations of immune and inflammatory cells in KTRs and Non-chronic kidney disease (non-CKD) controls over a longitudinal period are explored. Newly developed multi-colour flow cytometry methods were devised to identify and characterise immune cell populations. Twenty-six KTRs were randomised into one of two HIIT protocols or MICT: HIIT A (n=8; 4-, 2-, and 1-min intervals; 80-90% (V)over dotO(2peak)), HIIT B (n=8, 4x4 min intervals; 80-90% (V)over dotO(2peak)) or MICT (n=8, similar to 40 min; 50-60% (V)over dotO(2peak)) for 24 supervised sessions on a stationary bike (approx. 3x/week over 8 +/- 2 weeks). Blood samples taken pre-training, mid training, post-training and 3 months later. Novel multi-colour flow cytometric panels were developed to characterise lymphoid and myeloid cell population from peripheral blood mononuclear cells. No changes were observed for circulating immune and inflammatory cells over the 8-week interventions. This feasibility study does not suggest that exercise programmes using HIIT and MICT protocols elicit adverse negative effects on immunity in KTRs. Therefore, such protocols may be immunologically safe for these patients. The inability of the participants to achieve the target exercise intensities may be due to physiological abnormalities in this population which warrants further investigation.
Exercise, inflammation and acute cardiovascular events.
Individuals who participate in regular exercise over time have a markedly reduced risk of cardiovascular disease. Paradoxically, in susceptible individuals with underlying, often undiagnosed, disease states, exercise may acutely increase an individual's risk of cardiovascular events during and immediately following physical exertion. Exercise is thought to evoke conditions that trigger atheromatous plaque rupture or trigger life threatening arrhythmias in individuals with pre-existing, vulnerable coronary artery and inherited cardiovascular disease respectively. This transient increased risk may be driven by the inflammatory trigger provided by physical exertion where exercise is associated with an upregulation of inflammatory mediators in the acute phase. Conversely, habitual exercise can lead to a modulation of the inflammatory response over time. This review explores: exercise related inflammation; acute cardiovascular events related to exercise and strategies to mitigate these risks.
The effects of exercise on complement system proteins in humans: a systematic scoping review
Background: The complement system is comprised of the classical, lectin and alternative pathways that result in the formation of: pro-inflammatory anaphylatoxins; opsonins that label cells for phagocytic removal; and, a membrane attack complex that directly lyses target cells. Complement-dependent cytotoxicity (CDC) - cell lysis triggered by complement protein C1q binding to the Fc region of antibodies bound to target cells - is another effector function of complement and a key mechanism-of-action of several monoclonal antibody therapies. At present, it is not well established how exercise affects complement system proteins in humans. Methods: A systematic search was conducted to identify studies that included original data and investigated the association between soluble complement proteins in the blood of healthy humans, and: 1) an acute bout of exercise; 2) exercise training interventions; or, 3) measurements of habitual physical activity and fitness. Results: 77 studies were eligible for inclusion in this review, which included a total of 10,236 participants, and 40 complement proteins and constituent fragments. Higher levels of exercise training and cardiorespiratory fitness were commonly associated with reduced C3 in blood. Additionally, muscle strength was negatively associated with C1q. Elevated C3a-des-Arg, C4a-desArg and C5a, lower C1-inhibitor, and unchanged C3 and C4 were reported immediately post-laboratory based exercise, compared to baseline. Whereas, ultra-endurance running and resistance training increased markers of the alternative (factor B and H), classical (C1s), and leptin (mannose binding lectin) pathways, as well as C3 and C6 family proteins, up to 72-h following exercise. Heterogeneity among studies may be due to discrepancies in blood sampling/handling procedures, analytical techniques, exercise interventions/measurements and fitness of included populations. Conclusions: Increased anaphylatoxins were observed immediately following an acute bout of exercise in a laboratory setting, whereas field-based exercise interventions of a longer duration (e.g. ultra-endurance running) or designed to elicit muscle damage (e.g. resistance training) increased complement proteins for up to 72-h. C3 in blood was mostly reduced by exercise training and associated with increased cardiorespiratory fitness, whereas C1q appeared to be negatively associated to muscle strength. Thus, both acute bouts of exercise and exercise training appear to modulate complement system proteins. Future research is needed to assess the clinical implications of these changes, for example on the efficacy of monoclonal antibody therapies dependent on CDC.
Traumatic Brain Injury Rehabilitation: An Exercise Immunology Perspective
Traumatic brain injury (TBI) is the largest cause of death and disability globally. The physical and psychosocial consequences after TBI can persist for prolonged periods, and lead to increased health care and economic burden. Exercise has shown promise over recent years as a mode of rehabilitation that alleviates multiple TBI symptoms; but there is a lack of controlled large-scale studies and limited research into the underlying mechanisms. This critical review draws from animal and human studies on exercise immunology to speculate on possible mechanisms that could underlie beneficial outcomes of exercise after TBI. The anti-inflammatory role of exercise, protective role offered by pre-injury exercise, and the need for more objective studies on biomarker analysis are expected to be useful considerations to develop optimal post-TBI exercise rehabilitation programs. Future studies can consider investigating the specific immunological processes induced by exercise in consideration of individual differences and non-aerobic exercise modalities.
Immunometabolism-fit: How exercise and training can modify T cell and macro- phage metabolism in health and disease
Background: The term immunometabolism describes cellular and molecular metabolic processes that control the immune system and the associated immune responses. Acute exercise and regular physical activity have a substantial influence on the metabolism and the immune system, so that both processes are closely associated and influence each other bidirectionally.Scope of review: We limit the review here to focus on metabolic phenotypes and metabolic plasticity of T cells and macrophages to describe the complex role of acute exercise stress and regular physical activity on these cell types. The metabolic and immunological consequences of the social problem of inactivity and how, conversely, an active lifestyle can break this vicious circle, are then described. Finally, these aspects are evaluated against the background of an aging society.Major conclusions: T cells and macrophages show high sensitivity to changes in their metabolic environment, which indirectly or directly affects their central functions. Physical activity and sedentary behaviour have an important influence on metabolic status, thereby modifying immune cell phenotypes and influencing immunological plasticity. A detailed understanding of the interactions between acute and chronic physical activity, sedentary behaviour, and the metabolic status of immune cells, can help to target the dysregulated immune system of people who live in a much too inactive society.
Acute effects of heavy resistance exercise on biomarkers of neuroendocrine- immune regulation in healthy adults: a systematic review
Background: The nervous system integrates the immune system in the systemic effort to maintain or restore the organism's homeostasis. Acute bouts of exercise may alter the activity of specific pathways associated with neuroendocrine regulation of the immune system. Objective: To examine the acute effects of heavy resistance exercise on biomarkers of neuroendocrine-immune regulation in healthy adults.Methods: A systematic literature search was conducted using PubMed, Cochrane Controlled Trials Register, Web of Science and SportDiscus with no date restrictions up to March 2021. Clinical trials in English or German were included if they measured the blood plasma or serum concentrations of specific biomarkers of neuroendocrine-immune regulation (adrenaline, noradrenaline, acetylcholine, vasoactive intestinal peptide (VIP), cortisol, growth hormone, calcitonin gene -related peptide (CGRP), substance p, serotonin, brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF) or glia-derived neurotrophic factor (GDNF)) in a resting state prior to and no later than 60 minutes after an acute bout of heavy resistance exercise in healthy adults.Results: 7801 records were identified through literature search, of which 36 studies, with a total of 58 intervention groups, met the inclusion criteria. Evidence was found that an acute bout of heavy resistance exercise increased the levels of adrenaline (median: 185%), noradrenaline (median: 113%) and GH (median: 265%) immediately after the exercise. Mixed results were found for cortisol (median: 0%), suggesting that its response might be more sensitive to the configuration of the exercise scheme. The limited evidence regarding the effects on BDNF and ACTH allows no firm conclusions to be drawn about their response to heavy resistance exercise. The vast majority of the included studies reported a return of the biomarker concentrations to their baseline value within one hour after the termination of the exercise bout. No studies were identified that investigated the response of acetylcholine, VIP, CGRP, substance p, serotonin, NGF or GDNF to heavy resistance exercise.Conclusions: A bout of heavy resistance exercise alters the circulating concentrations of selected biomarkers of neuroendocrine-immune regulation. Both subject characteristics, such as sex as well as exercise parameters, such as rest intervals appear to have the potential to influence these effects.
The effect of exercise on regulatory T cells: A systematic review of human and animal studies with future perspectives and methodological recommendations
Many of the exercise-related health-promoting effects are attributed to beneficial immunomodulation. The restoration of immune homeostasis is context-dependent, meaning either to increase anti-inflammatory signaling to counteract disease progression of non-communicable (auto)inflammatory diseases or to enhance (local) activity of proinflammatory immune cells to slow down or inhibit cancer progression. Regulatory CD4+ T cells (T regs) represent the main regulatory component of the adaptive immune system that fine-tunes inflammatory responses, keeps them in check and prevents long-lasting autoimmunity. Because often dysregulated in the context of various diseases, emerging treatment approaches aim to modulate their number or inherent anti-inflammatory and immunosuppressive function in a highly disease-specific way. Exercise represents a non-pharmacologic strategy in disease prevention and rehabilitation and may be an effective treatment with few to no side effects to counteract dysregulation of T regs. To date, several studies have evaluated the effect of exercise on T reg-related outcomes. This review aims at providing a comprehensive overview on alterations of blood- or tissue-derived T reg counts, proportion and functionality following acute and chronic exercise in humans and animal models. From the 60 reviewed studies, an overall disease-specific beneficial effect of chronic exercise on T reg levels in animal models can be stated, while both acute and chronic effects in human studies are less definite. However, T reg phenotyping is less sufficient in the animal studies compared to human studies. Only a limited number of studies investigated T reg functionality. There is a large heterogeneity concerning study design, human population or animal model, exercise protocol, and T reg outcome measure specification which makes it difficult to compare results and draw clear conclusions. Study results are discussed in the context of current concepts in exercise immunology. Finally, future perspectives and methodological recommendations are provided to promote research in this field.
EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS
Copyright (c) 2021 Exercise Immunology Review https://rightsstatements.org/page/InC/1.0/
Exercise training effects on natural killer cells: a preliminary proteomics and systems biology approach
Background: Regular exercise, particularly moderate-intensity continuous training (MICT), can improve immune function. Natural killer (NK) cells, a subset of lymphocytes that react to infections, are the most responsive innate immune cells to exercise, but the mechanisms underlying this are poorly understood. A type of exercise training that is gaining popularity in recent years is high-intensity interval training (HIIT), but how it affects NK cells is largely unknown. In fact, intense exercise has been traditionally viewed as a potential stressor to immune homeostasis. The purpose of this study was to determine in healthy, previously untrained adults (N=8 [3 male; 40 +/- 6 years]) the effects of an intervention consisting of 4-week MICT followed by 4-week HIIT on NK cells as compared with a pre-training (baseline) state. Methods: Participants were studied at three time points: baseline, mid-intervention (after MICT), and post-intervention (after HIIT). Main assessments included cytotoxicity assays, flow-cytometry analysis of NK cell surface markers, and interrogation of the cellular proteome using a systems biology approach. Results: A significant time effect was found for NK cell cytotoxicity (p<0.001), which was increased similar to 10-fold at both midand post-intervention versus baseline. No significant intervention effect was found for NK surface receptor expression, except for CXCR3 determined as mean fluorescence intensity (p=0.044, although with no significant differences in post hoc pairwise comparisons). The proteins showing a higher differential expression (Log2 fold-change>10 and false discovery rate [FDR] q-value<0.001) were COP9 signalosome subunit 3 (COPS3), DnaJ heat shock protein family member B11 (DNAJB11), histidyl-TRNA synthetase 1 (HARS), NIMA related kinase 9 (NEK9), nucleoporin 88 (NUP88), phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1), regulator of chromosome condensation 2 (RCC2), TAO kinase 3 (TAOK3), transducin beta like 2 (TBL2), and ring finger protein 40 (RNF40). All were upregulated at mid-intervention compared with baseline, with the exception of HARS, which was downregulated. Four enriched pathways (FDR <25%) were found: two related to transmembrane transport and cellular composition (downregulated at mid-intervention vs baseline), and two related to oxidation-reduction reactions (upregulated at post-intervention versus baseline). Conclusions: A progressive exercise intervention of MICT followed by HIIT induces a remarkable improvement in NK function compared with the untrained state, although at the mechanistic level the pathways involved seem to differ over time during the intervention.
A systematic literature review on the effects of exercise on human Toll-like receptor expression
Background Toll-like receptors (TLRs) are a family of transmembrane pattern recognition receptors that are mainly expressed on immune cells. Recognition of various exogenous and endogenous molecular patterns activates the TLR signalling cascade, which orchestrates an inflammatory immune response. Dysfunctional immune responses, including aberrant TLR signalling, are increasingly implicated in the associations between sedentarism, chronic low-grade systemic inflammation and various non-communicable diseases. Conversely, exercise exerts anti-inflammatory effects, which could be conferred through its immunomodulatory properties, potentially affecting TLRs. This study aims to systematically review the effects of exercise on human TLR expression. Method A systematic literature search of Pubmed, Embase, The Cochrane Library and SPORTDiscus for articles addressing the impact of exercise (as isolated intervention) on TLRs in humans was conducted, ending in February 2020. Results A total of 66 articles were included. The publications were categorised according to exercise modality and duration: acute resistance exercise (4 studies), acute aerobic exercise (26 studies), resistance training program (9 studies), aerobic training program (16 studies), combined (i.e. resistance and aerobic) training program (8 studies) and chronic exercise not otherwise classifiable (9 studies). Five articles investigated more than one of the aforementioned exercise categories. Several trends could be discerned with regard to the TLR response in the different exercise categories. Acute resistance exercise seemed to elicit TLR upregulation, whereas acute aerobic exercise had less activating potential with the majority of responses being neutral or, especially in healthy participants, downregulatory. Chronic resistance and combined exercise programs predominantly resulted in unaltered or decreased TLR levels. In the chronic aerobic exercise category, mixed effects were observed, but the majority of measurements demonstrated unchanged TLR expression. Conclusion Currently published research supports an interplay between exercise and TLR signalling, which seems to depend on the characteristics of the exercise. However, there was large heterogeneity in the study designs and methodologies. Therefore, additional research is required to further corroborate these findings, to define its pathophysiological implications and to elucidate the mechanism(s) linking exercise to TLR signalling.
Improvement in the anti-inflammatory profile with lifelong physical exercise is related to clock genes expression in effector-memory CD4+T cells in master athletes.
Purpose: Ageing is associated with alterations in the immune system as well as with alterations of the circadian rhythm. Immune cells show rhythmicity in execution of their tasks. Chronic inflammation (inflammaging), which is observed in the elderly, is mitigated by lifelong exercise. The aimed this study was to determine the acute effect of a maximal exercise test on clock genes, regulatory proteins and cytokine expression, and evaluate the effect of lifelong exercise on the expression of clock genes in subpopulations of effector-memory (EM) CD4+ and CD8+T cells and the association of these processes with the inflammatory profile. Therefore, this study aimed to investigate the expression of clock genes in subpopulations of effector memory (EM) CD4+ and CD8+ T cells in master athletes and healthy controls and further associate them with systemic inflammatory responses to acute exercise. Methods: The study population comprised national and international master athletes (n = 18) involved in three sports (athletics, swimming and judo). The control group (n = 8) comprised untrained healthy volunteers who had not participated in any regular and competitive physical exercise in the past 20 years. Anthropometric measurements and blood samples were taken before (Pre), 10 min after (Post) and 1 h after (1 h Post) a maximal cycle ergometer test for the determination of maximum oxygen consumption (VO 2 max). The subpopulations of EM CD4+ and CD8+ T cells were purified using fluorescenceactivated cell sorting. RNA extraction of clock genes (CLOCK, BMAL1, PER1, PER2, CRY1, CRY2, REV-ERBa, REV-ERB ss, RORa, RORb and RORc) in EM CD4+ and EM CD8+ T cells as well as regulatory proteins (IL-4, IFN-., Tbx21, PD-1, Ki67, NF-kB, p53 and p21) in EM CD4+ T cells was performed. The serum concentration of cytokines (IL-8, IL-10, IL-12p70 and IL-17A) was measured. Results: The master athletes showed better physiological parameters than the untrained healthy controls (P<0.05). The levels of cytokines increased in master athletes at Post compared with those at Pre. The IL-8 level was higher at 1 h Post, whereas the IL-10 and IL-12p70 levels returned to baseline. There was no change in IL-17A levels (P< 0.05). The clock genes were modulated differently in CD4+ T cells after an acute session of exercise in a training status-dependent manner. Conclusion: The synchronization of clock genes, immune function and ageing presents new dimensions with interesting challenges. Lifelong athletes showed modified expression patterns of clock genes and cytokine production associated with the physical fitness level. Moreover, the acute bout of exercise altered the clock machinery mainly in CD4+ T cells; however, the clock gene expressions induced by acute exercise were different between the master athletes and control group.
Higher levels of physical activity are associated with reduced tethering and migration of pro-inflammatory monocytes in males with central obesity
Despite evidence that monocyte migration is accentuated by central adiposity, the impact of physical activity (PA) and exercise, particularly in the post-prandial state, on limiting migration are not established. We hypothesised that PA and a single bout of walking exercise would be associated with reduced ex vivo monocyte tethering and migration in middleaged males with central obesity (CO). Objective levels of PA were measured for 7 days in lean males (LE, N=12, mean (SD) age 39 (10) years, waist circumference 81.0 (6.3) cm) and males with CO (N=12, mean (SD) age 40 (9) years, waist circumference 115.3 (13.9) cm), followed by donation of a fasted blood sample. On the same day, CO undertook a bout of walking exercise, before donation of a second fasted blood sample. An ex vivo assay, coupled to flow cytometry, determined tethering and migration of classical, intermediate, and non-classical monocytes. C-C and CXC chemokine receptor (CCR2, CCR5 and CX3CR1) expression were also determined on total and classical monocytes. Monocyte subsets (total, classical, intermediate and CCR2+ monocytes), metabolic (glucose and lipids) and inflammatory (C-reactive protein) markers were greater in CO vs. LE (lower highdensity lipoprotein); however, adjustments for PA mitigated group differences for glucose, lipids, and monocyte subsets. Ex vivo tethering and migration (absolute and relative) of most monocyte subsets was greater in CO vs LE. Relative monocyte tethering and migration was largely not influenced by PA; however, higher PA was associated with reduced absolute migration and tethering of CD16 expressing monocytes in CO. Prior walking had no impact on these variables. These results highlight that regular PA, not single exercise bouts may limit the migration of pro-inflammatory monocytes in CO. These changes may relate to physiological parameters in blood (i.e. number of cells and their adhesion), rather than differences in chemokine receptor expression.
Regular physical exercise mediates the immune response in atherosclerosis
Atherosclerosis is a chronic inflammatory cardiovascular disease, which results from lipid accumulation in the blood vessel wall, forming a plaque, and ultimately restricting blood flow. The immune system plays a vital role in progression to plaque rupture. While recent evidence clearly indicates the anti-inflammatory function of regular exercise, the mechanisms by which regular exercise can modulate its pathophysiology is not well understood. In this review, we discuss how regular exercise can lower systemic inflammation directly via modulation of the immune system or indirectly via altered myokine concentrations and metabolites. We describe the exercise-induced responses of various myokines (such as IL-6, adiponectin, and FGF21), and how cell function in the innate immune system can be modulated via regular exercise, with the aim to modulate plaque formation in atherosclerosis.
Physical Exercise: A Versatile Anti-Inflammatory Tool Involved in the Control of Hypothalamic Satiety Signaling
"The hypothalamus plays a critical role in the control of food consumption and energy expenditure. Fatty diets can elicit an inflammatory response in specific hypothalamic cells, including astrocytes, tanycytes, and microglia, disrupting anorexigenic signals in region-specific hypothalamic neurons, contributing to overeating and body weight gain. In this study, we present an update regarding the knowledge of the effects of physical exercise on inflammatory signaling and circuits to control hunger in the hypothalamus in obesity conditions. To try to understand changes in the hypothalamus, we review the use of magnetic resonance/anorexigenic hormone analysis in humans, as well as in animal models to explore the physiological and molecular mechanism by which exercise modulates satiety signals, such as the central antiinflammatory response, myokine delivery from skeletal muscle, and others. The accumulation of scientific evidence in recent years allows us to understand that exercise contributes to weight control, and it is managed by mechanisms that go far beyond ""burning calories."""
Effect of exercise-conditioned human serum on the viability of human cancer cell cultures: A systematic review and meta-analysis
Numerous epidemiological studies have shown the existence of a relationship between exercise and a reduced risk of different types of cancer. In vitro studies have identified a direct effect of exercise-conditioned human serum on cancer cell lines of the lung, breast, prostate, and colon. The aim of this systematic review with meta-analysis (SRM) was to estimate the magnitude of the effect that exercise-conditioned human serum produced on the viability of human cancer cell cultures. The design followed the PRISMA guidelines and the TREND statement to assess the quality of information (QoI) in each study. Nine in vitro studies were included in the SRM, involving a total of nine cancer cell lines and serum from 244 individuals from different countries, including namely healthy sedentary individuals, at risk of prostate cancer individuals and cancer patients, with ages ranging from 18 to 73 years. The impact of acute exercise-conditioned human serum on the viability of cancer cell cultures was analysed by a variety of assays, using pre-exercise human serum for comparison purposes. Globally, cultures of cancer cell lines exposed to human serum conditioned by acute exercise of various intensities exhibited a reduced viability, when compared with control cultures, with an overall effect size (ES) of -1.126 (95% CI; -1.300 to -0.952; p < 0.001). When the analysis only included human serum conditioned by acute high-intensity exercise, the effect became more pronounced (ES -1.350; -1.522 to -1.179 (95% CI); p < 0.001). These results are in line with the hypothesis that changes in human serum induced by exercise might play a role in the beneficial effects of physical activity in cancer prevention and management and that these effects depend on exercise intensity.