Exercise Immunology Review最新文献

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 naïve helper (CD4+) and cytotoxic (CD8+) T cells and peripheral blood mononuclear cells (PBMCs) in response to prolonged cycling.

Methods: Tenaerobically 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 naïve CD4+ and CD8+ T cells were determined using extracellular flux analysis. Mitochondrial membrane potential (ΔΨm) 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 naïve T cells across all timepoints, but not PBMCs in recovery. This was despite absolute and relative changes in ΔΨm 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 naïve T cells and PBMCs were largely unaltered within 2 hours of prolonged moderate intensity cycling.

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.

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 naïve, 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, and MDA-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 with stretching may affect the inflammatory profile, possibly due to a higher overall inflammatory status.

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.

Exercise represents a non-pharmacological strategy capable of concurrently modulating tumor metabolism and immunity. Regular physical activity reprograms systemic and tumorlocalized 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-HIF1α, PGC-1α-ERRα, 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.

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 in 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 to 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.

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 not find 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, and EBSCOhost, 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 noncontrolled 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 with 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 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: Protocol registration on in the International Prospective Register of Systematic Reviews (PROSPERO): CRD42022380991.

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 SARSCoV-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.

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.

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.