Exercise Immunology Review最新文献

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 setpoint, but stimulating this response of the immune system in healthy individuals.

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.

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-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-α (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 of 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 in sTNFR2 (ES:-0.997) and an increase in BDNF (ES:1.412). Locally, intra-articular IL-10 (ES:9.163) increased, and IL1β (ES:-6.199) and TNF-α 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-α:-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 antiinflammatory properties have important implications for informing these patients and clinicians about the underlying effects of ET.

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 cirulating 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.

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.

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-des-Arg 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.

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 potential 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 systematic review on PubMed, Scopus, Embase, Web of Science, Cochrane 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 contrast, 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 infection 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.

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 tradional 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 physiolocial and immunological impact of 8-weeks of HIIT and moderate intensity continuous training (MICT) in kidney transplan recipients (KTRs). In addition, the natural variations of immune and inflammatory cells in KTRs and 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% VO2peak), HIIT B (n=8, 4x4 min intervals; 80-90% VO2peak), or MICT (n=8, ~40 min; 50-60% VO2peak) 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. The 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.

Numerous epidemiological studies have shown the existence of a relationship between exercise and 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 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 exerciseconditioned 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 exercise of various intensities exhibited a reduced viability, when compared with control cultures, with an overall effect size of -1.126 (95% CI; -1.300 to -0.952; p < 0.001). When the analysis only included human serum conditioned by 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.

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.