Physical exercise, the immune system and infection risk: implications for prehabilitation and rehabilitation for solid organ transplantation candidates and recipients.

PURPOSE OF REVIEW: Solid organ transplantation recipients have an increased risk of infection, exacerbated by immunosuppressant medications that need to finely balance suppression of the immune system to prevent allograft rejection while avoiding over-suppression leading to infections and malignancy. Exercise modulates immune functions, with moderate-intensity activities particularly associated with enhanced antiviral immunity and reduced infection incidence. However, investigations of the effects of exercise and physical activity on immune function and infection risk posttransplantation are scarce. This review highlights areas where the relationship between exercise, immune function and infection risk has greatest potential for benefit for solid organ transplantation and therefore greatest need for investigation. RECENT FINDINGS: Moderate and higher intensity exercise do not appear to cause adverse immunological effects in kidney transplantation recipients, although evidence from other organ transplantation is lacking. Evidence from healthy younger and older adults suggests that regular exercise can reduce risk of respiratory infections and latent herpesvirus reactivation and improves antibody responses to vaccination, which is of great importance for organ transplantation recipients. SUMMARY: There is a strong need for research to investigate the role of exercise on immune function and infection risk in solid organ transplantation to improve both allograft survival and long-term health of the recipient.

Combined effects of green tea supplementation and eccentric exercise on nuclear factor erythroid 2-related factor 2 activity.

PURPOSE: This study investigated whether combining eccentric exercise and green tea supplementation synergistically increased nuclear factor erythroid 2-related factor 2 (NRF2) activity, a transcription factor responsible for coordinating endogenous antioxidant expression. METHODS: In a double-blinded, randomized, between-subjects design, 24 males (mean [SD]; 23 [3] years, 179.6 [6.1] cm, 78.8 [10.6] kg) performed 100 drop jumps following a 6 days supplementation period with either green tea (poly)phenols (n = 12; 500 mg·d-1) or a placebo (n = 12; inulin). NRF2/antioxidant response element (ARE) binding in peripheral blood mononuclear cells (PBMCs), catalase (CAT) and glutathione reductase (GR) activity, 8-hydroxy-2'-deoxyguanosine (8-OHdG) excretion, and differential leukocyte counts were measured pre-, post-, 1 h and 24 h post-exercise. RESULTS: Exercise did not increase NRF2/ARE binding (p = 0.12) (fold change vs rest: green tea = [post] 0.78 ± 0.45, [1 h] 1.17 ± 0.54, [24 h] 1.06 ± 0.56; placebo = [post] 1.40 ± 1.50, [1 h] 2.98 ± 3.70, [24 h] 1.04 ± 0.45). Furthermore, CAT activity (p = 0.12) and 8-OHdG excretion (p = 0.42) were unchanged in response to exercise and were not augmented by green tea supplementation (p > 0.05 for all). Exercise increased GR activity by 30% (p = 0.01), however no differences were found between supplement groups (p = 0.51). Leukocyte and neutrophil concentrations were only elevated post-exercise (p < 0.001 for all). CONCLUSION: Eccentric exercise, either performed alone or in conjunction with green tea supplementation, did not significantly increase NRF2 activity in PBMCs. TRIAL REGISTRATION NUMBER: osf.io/kz37g (registered: 15/09/21).

Frequently Interrupting Prolonged Sitting With Light Body-Weighted Resistance Activity Alters Psychobiological Responses to Acute Psychological Stress: A Randomized Crossover Trial.

BACKGROUND: Uninterrupted prolonged sitting and exaggerated psychobiological reactivity to acute psychological stress are associated with increased risk of cardiovascular disease (CVD). Breaking up prolonged sitting with frequent, short bouts of light-intensity physical activity acutely lowers CVD risk markers under resting conditions. PURPOSE: To examine whether frequent interruptions to prolonged sitting with body-weighted resistance activity can acutely lower systolic blood pressure (SBP; primary outcome) and other cardiovascular (CV), inflammatory, and cortisol (secondary outcomes) responses to acute psychological stress. METHODS: This randomized crossover trial included 17 sedentary participants (9 men; mean ± SD age; 24.0 ± 0.5 years) who completed two conditions: (i) interrupting 4 hr of sitting with 4 min of light body-weighted resistance activity every 30-min (BREAK), and (ii) 4 hr of uninterrupted sitting (SIT). Following the BREAK and SIT intervention windows, CV, inflammatory, and cortisol markers were measured at rest, during stress tasks (8-min Paced Auditory Serial Addition Test [PASAT] and 3-min cold pressor [CP]), and 45-min recovery periods. RESULTS: There were main effects of time for CV parameters (SBP, diastolic blood pressure, heart rate, cardiac output, and total peripheral resistance [all p < .001]), inflammatory markers (interleukin-6 [IL-6]), and cortisol (p < .05) in response to stress. Time-by-condition interaction effects revealed that in the BREAK-condition there was lower SBP during immediate recovery from the CP (mean {95% confidence interval [CI]}: 127.2 [121.3, 133.4] vs 133.4 [125.5, 141.7] mmHg; p = .020), higher concentrations of plasma IL-6 45-min post-PASAT (2.70 [1.97, 3.70] vs 1.71 [1.32, 2.22] pg/mL; p = .010), and larger (nonsignificant) salivary cortisol concentrations 8-min post-CP (6.29 [4.60, 8.58] vs 3.97 [3.16, 4.99] nmol/L; p = .079). CONCLUSIONS: Interrupting prolonged sitting with frequent bouts of light intensity body-weighted resistance activity alters psychobiological responses to acute psychological stress. Further research should explore the longer-term implications for CVD risk.

Sitting for long periods without interruption and the way in which we physically respond to short-term psychological stress are linked to heart disease risk. Breaking up sitting with short, frequent bouts of light activity can lower heart disease risk but how this may improve how we respond to stress is unknown. Our study investigated if interruptions to prolonged sitting with body-weighted resistance activity lowered changes seen under stress such as changes in blood pressure (BP) and inflammation. Seventeen participants undertook two testing sessions. One session interrupted 4 hr of sitting with 4-min of light activity every 30-min, and the other session was 4 hr of uninterrupted sitting. After each session, participants did two stress tasks: one math-based task and one where feet were submerged in cold water. The changes in BP and inflammation to stress were measured. We found when breaking-up sitting time with activity, BP was lower after the cold-water task compared to when people did not break up their sitting. In summary, breaking up sitting with frequent bouts of light activity may influence how we respond to short-term stress, but future research needs to explore what these short-term changes mean for the longer-term risks of heart disease.

Device-assessed sleep and physical activity in individuals recovering from a hospital admission for COVID-19: a multicentre study.

BACKGROUND: The number of individuals recovering from severe COVID-19 is increasing rapidly. However, little is known about physical behaviours that make up the 24-h cycle within these individuals. This study aimed to describe physical behaviours following hospital admission for COVID-19 at eight months post-discharge including associations with acute illness severity and ongoing symptoms. METHODS: One thousand seventy-seven patients with COVID-19 discharged from hospital between March and November 2020 were recruited. Using a 14-day wear protocol, wrist-worn accelerometers were sent to participants after a five-month follow-up assessment. Acute illness severity was assessed by the WHO clinical progression scale, and the severity of ongoing symptoms was assessed using four previously reported data-driven clinical recovery clusters. Two existing control populations of office workers and individuals with type 2 diabetes were comparators. RESULTS: Valid accelerometer data from 253 women and 462 men were included. Women engaged in a mean ± SD of 14.9 ± 14.7 min/day of moderate-to-vigorous physical activity (MVPA), with 12.1 ± 1.7 h/day spent inactive and 7.2 ± 1.1 h/day asleep. The values for men were 21.0 ± 22.3 and 12.6 ± 1.7 h /day and 6.9 ± 1.1 h/day, respectively. Over 60% of women and men did not have any days containing a 30-min bout of MVPA. Variability in sleep timing was approximately 2 h in men and women. More severe acute illness was associated with lower total activity and MVPA in recovery. The very severe recovery cluster was associated with fewer days/week containing continuous bouts of MVPA, longer total sleep time, and higher variability in sleep timing. Patients post-hospitalisation with COVID-19 had lower levels of physical activity, greater sleep variability, and lower sleep efficiency than a similarly aged cohort of office workers or those with type 2 diabetes. CONCLUSIONS: Those recovering from a hospital admission for COVID-19 have low levels of physical activity and disrupted patterns of sleep several months after discharge. Our comparative cohorts indicate that the long-term impact of COVID-19 on physical behaviours is significant.

Sedentary behaviour is associated with heightened cardiovascular, inflammatory and cortisol reactivity to acute psychological stress.

BACKGROUND: Sedentary behaviour is a risk factor for cardiovascular disease (CVD), but the underlying mechanisms remain unclear. Exaggerated psychobiological responses to acute psychological stress increase CVD risk. Sedentary behaviour is associated with characteristics that can predict large psychobiological stress response patterns (e.g., elevated resting blood pressure and systemic inflammation), but it is currently unknown whether sedentary behaviour and stress reactivity are directly linked. The aim of this study was to examine associations between device-assessed sedentary behaviour and measures of stress reactivity. METHODS: Sixty-one healthy adults wore an activPAL (thigh) and ActiGraph (wrist) for seven days to measure habitual levels of sedentary behaviour (mean ± SD = 9.96 ± 1.48 h/day) and moderate-to-vigorous physical activity (mean ± SD = 101.82 ± 42.92 min/day). Participants then underwent stress reactivity testing, where beat-to-beat cardiovascular (e.g., blood pressure, total peripheral resistance), inflammatory (plasma interleukin-6, leukocytes) and salivary cortisol measurements were taken in response to an 8-minute socially evaluative Paced Auditory Serial Addition Test. RESULTS: Higher volumes of daily sedentary behaviour were associated with larger stress responses for diastolic blood pressure (Β=1.264, 95%CI=0.537-1.990, p = .005), total peripheral resistance (Β=40.563, 95%CI=19.310-61.812, p < .001), interleukin-6 (Β=0.219, 95%CI=0.109-0.329, p < .001) and cortisol (Β=1.844, 95%CI=1.139-2.549, p < .001). These findings emerged independent of a priori determined covariates, including daily levels of moderate-to-vigorous physical activity and adiposity. DISCUSSION: Exaggerated stress reactivity is characteristic of high sedentary behaviour and could be a novel mechanism linking sedentary behaviour with CVD. Future work should examine the impact of reducing sedentary behaviour on measures of stress reactivity, as this may have clinical relevance for preventing CVD.

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 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.

Lifestyle modification and inflammation in people with axial spondyloarthropathy-A scoping review.

INTRODUCTION: People with axial spondyloarthritis (AS) have an inflammatory profile, increasing the risk of hypertension, type 2 diabetes, obesity, and dyslipidaemia. Consequently, AS is linked with co-morbidities such as cardiovascular disease (CVD). Physical inactivity, diet, smoking, alcohol consumption, and obesity influence inflammation, but knowledge of the interaction between these with inflammation, disease activity, and CVD risk in AS is dominated by cross-sectional research. METHODS: A review of the literature was conducted between July 2020 and December 2021. The focus of the scoping review is to summarise longitudinal and randomised control trials in humans to investigate how tracking or modifying lifestyle influences inflammation and disease burden in patients with AS. KEY MESSAGES: (1) Lifestyle modifications, especially increased physical activity (PA), exercise, and smoking cessation, are critical in managing AS. (2) Smoking is negatively associated with patient reported outcome measures with AS, plus pharmaceutical treatment adherence, but links with structural radiographic progression are inconclusive. (3) Paucity of data warrant structured studies measuring inflammatory cytokine responses to lifestyle modification in AS. CONCLUSION: Increased PA, exercise, and smoking cessation should be supported at every given opportunity to improve health outcomes in patients with AS. The link between smoking and radiographic progression needs further investigation. Studies investigating the longitudinal effect of body weight, alcohol, and psychosocial factors on disease activity and physical function in patients with AS are needed. Given the link between inflammation and AS, future studies should also incorporate markers of chronic inflammation beyond the standard C-reactive protein and erythrocyte sedimentation rate measurements.

Circulating endotoxin and inflammation: associations with fitness, physical activity and the effect of a 6-month programme of cycling exercise during haemodialysis.

BACKGROUND: Intradialytic cycling (IDC) may provide cardiovascular benefits to individuals receiving haemodialysis, but the exact mechanism behind these improvements remains unclear. The primary aim of this study was to investigate the effect of a 6-month programme of IDC on circulating endotoxin (secondary analysis from the CYCLE-HD trial). Secondary aims were to investigate changes in circulating cytokines [interleukin-6 (IL-6), IL-10, tumour necrosis factor-α, C-reactive protein (CRP) and the IL-6:IL-10 ratio] and their associations with physical activity, fitness and cardiovascular outcomes. METHODS: Participants were randomized to either a 6-month programme of IDC (thrice weekly, moderate intensity cycling at a rating of perceived exertion of 12-14) in addition to usual care (n = 46) or usual care only (control group; n = 46). Outcome measures were obtained at baseline and then again at 6 months. RESULTS: There was no significant (P = 0.137) difference in circulating endotoxin between groups at 6 months (IDC group: 0.34 ± 0.08 EU/mL; control group: 0.37 ± 0.07 EU/mL). There were no significant between-group differences in any circulating cytokine following the 6-month programme of IDC. Higher levels of physical activity and fitness were associated with lower levels of endotoxin, IL-6, CRP and IL-6:IL-10 ratio. CONCLUSIONS: Our data show no change in circulating endotoxin or cytokines following a 6-month programme of IDC. However, higher levels of physical activity outside of haemodialysis were associated with lower levels of inflammation.

Acute Running and Coronary Heart Disease Risk Markers in Male Cigarette Smokers and Nonsmokers: A Randomized Crossover Trial.

PURPOSE: Cigarette smoking is an independent risk factor for coronary heart disease and is associated with impaired postprandial metabolism. Acute exercise reduces postprandial lipemia and improves other coronary heart disease risk markers in nonsmokers. Less is known about responses in cigarette smokers. METHODS: Twelve male cigarette smokers (mean ± SD; age = 23 ± 4 yr, body mass index = 24.9 ± 3.0 kg·m-2) and 12 male nonsmokers (age = 24 ± 4 yr, body mass index = 24.1 ± 2.0 kg·m-2) completed two, 2-d conditions (control and exercise) in a randomized crossover design. On day 1, participants rested for 9 h (0800-1700) in both conditions except a 60-min treadmill run (65% ± 7% peak oxygen uptake, 2.87 ± 0.54 MJ) was completed between 6.5 and 7.5 h (1430-1530) in the exercise condition. On day 2 of both conditions, participants rested and consumed two high-fat meals over 8 h (0900-1700) during which 13 venous blood samples and nine resting arterial blood pressure measurements were collected. RESULTS: Smokers exhibited higher postprandial triacylglycerol and C-reactive protein than nonsmokers (main effect group effect size [Cohen's d] ≥ 0.94, P ≤ 0.034). Previous day running reduced postprandial triacylglycerol, insulin, and systolic and diastolic blood pressure (main effect condition d ≥ 0.28, P ≤ 0.044) and elevated postprandial nonesterified fatty acid and C-reactive protein (main effect condition d ≥ 0.41, P ≤ 0.044). Group-condition interactions were not apparent for any outcome across the total postprandial period (0-8 h; all P ≥ 0.089), but the exercise-induced reduction in postprandial triacylglycerol in the early postprandial period (0-4 h) was greater in nonsmokers than smokers (-21%, d = 0.43, vs -5%, d = 0.16, respectively; group-condition interaction P = 0.061). CONCLUSIONS: Acute moderate-intensity running reduced postprandial triacylglycerol, insulin, and resting arterial blood pressure the day after exercise in male cigarette smokers and nonsmokers. These findings highlight the ability of acute exercise to augment the postprandial metabolic health of cigarette smokers and nonsmokers.

Fasted plasma asprosin concentrations are associated with menstrual cycle phase, oral contraceptive use and training status in healthy women.

PURPOSE: Asprosin, an orexigenic hormone that stimulates hepatic glucose release, is elevated in insulin resistance and associated with obesity. Plasma asprosin concentrations may also be related to female sex hormone levels; higher levels are reported in women with polycystic ovary syndrome (PCOS) but this may be related to peripheral insulin resistance also associated with PCOS. Clarification of female-specific factors influence on the plasma asprosin response is crucial for studies investigating asprosin. Therefore, this study determined the association of menstrual phase, oral contraceptive (OC) use (as a pharmacological influence on sex hormone levels) and training status (as a physiological influence on sex hormone levels) on plasma asprosin levels in pre-menopausal women. METHODS: Fasting plasma asprosin, 17ß-estradiol (E2) and progesterone, were assessed in 32 healthy untrained and trained women with regular menstrual cycles (non-OC; n = 8 untrained, n = 6 trained) or using OC (n = 10 untrained, n = 8 trained) during early follicular, late follicular and mid-luteal menstrual phases (or the time-period equivalent for OC users). RESULTS: Asprosin was lower in OC (0.75 ± 0.38 ng mL-1) than non-OC users (1.00 ± 0.37 ng mL-1; p = 0.022). Across a cycle, asprosin was highest in the early follicular equivalent time-point in OC users (0.87 ± 0.37 ng mL-1) but highest in the mid-luteal phase in non-OC users (1.09 ± 0.40 ng mL-1). Asprosin concentrations varied more across a cycle in untrained than trained women, with higher concentrations in the early follicular phase compared to the late follicular and mid-luteal (training status-by-menstrual phase interaction p = 0.028). CONCLUSION: These findings highlight the importance of considering OC use, menstrual cycle phase and to a lesser extent training status when investigating circulating asprosin concentrations in females.

Short-term High-fat Overfeeding Does Not Induce NF-κB Inflammatory Signaling in Subcutaneous White Adipose Tissue.

CONTEXT: It is unclear how white adipose tissue (WAT) inflammatory signaling proteins respond during the early stages of overnutrition. OBJECTIVE: To investigate the effect of short-term, high-fat overfeeding on fasting abdominal subcutaneous WAT total content and phosphorylation of proteins involved in nuclear factor-κB (NF-κB) inflammatory signaling, systemic metabolic and inflammatory biomarkers. DESIGN: Individuals consumed a high-fat (65% total energy from total fat), high-energy (50% above estimated energy requirements) diet for 7 days. RESULTS: Fifteen participants (aged 27 ± 1 years; body mass index 24.4 ± 0.6 kg/m2) completed the study. Body mass increased following high-fat overfeeding (+1.2 ± 0.2 kg; P < 0.0001). However, total content and phosphorylation of proteins involved in NF-κB inflammatory signaling were unchanged following the intervention. Fasting serum glucose (+0.2 ± 0.0 mmol/L), total cholesterol (+0.4 ± 0.1 mmol/L), low-density lipoprotein cholesterol (+0.3 ± 0.1 mmol/L), high-density lipoprotein cholesterol (+0.2 ± 0.0 mmol/L), and lipopolysaccharide-binding protein (LBP; +4.7 ± 2.1 µg/mL) increased, whereas triacylglycerol concentrations (-0.2 ± 0.1 mmol/L) decreased following overfeeding (all P < 0.05). Systemic biomarkers (insulin, soluble cluster of differentiation 14 [CD14], C-reactive protein, interleukin-6, tumor necrosis factor-α and monocyte chemoattractant protein-1) and the proportion and concentration of circulating CD14+ monocytes were unaffected by overfeeding. CONCLUSION: Acute lipid oversupply did not impact on total content or phosphorylation of proteins involved in WAT NF-κB inflammatory signaling, despite modest weight gain and metabolic alterations. Systemic LBP, which is implicated in the progression of low-grade inflammation during the development of obesity, increased in response to a 7-day high-fat overfeeding period.

Elevating body termperature to reduce low-grade inflammation: a welcome strategy for those unable to exercise?

Chronic low-grade inflammation is increasingly recognized in the aetiology of a range of chronic diseases, including type 2 diabetes mellitus and cardiovascular disease, and may therefore serve as a promising target in their prevention or treatment. An acute inflammatory response can be induced by exercise; this is characterised by the acute increase in proinflammatory markers that subsequently stimulate the production of anti-inflammatory proteins. This may help explain the reduction in basal concentrations of pro-inflammatory markers following chronic exercise training. For sedentary populations, such as people with a disability, wheelchair users, or the elderly, the prevalence of chronic low-grade inflammation- related disease is further increased above that of individuals with a greater capacity to be physically active. Performing regular exercise with its proposed anti-inflammatory potential may not be feasible for these individuals due to a low physical capacity or other barriers to exercise. Therefore, alternatives to exercise that induce a transient acute inflammatory response may benefit their health. Manipulating body temperature may be such an alternative. Indeed, exercising in the heat results in a larger acute increase in inflammatory markers such as interleukin-6 and heat shock protein 72 when compared with exercising in thermoneutral conditions. Moreover, similar to exercise, passive elevation of body temperature can induce acute increases and chronic reductions in inflammatory markers and positively affect markers of glycaemic control. Here we discuss the potential benefits and mechanisms of active (i.e., exercise) and passive heating methods (e.g., hot water immersion, sauna therapy) to reduce chronic low-grade inflammation and improve metabolic health, with a focus on people who are restricted from being physically active.

Characterization of extracellular redox enzyme concentrations in response to exercise in humans.

Redox enzymes modulate intracellular redox balance and are secreted in response to cellular oxidative stress, potentially modulating systemic inflammation. Both aerobic and resistance exercise are known to cause acute systemic oxidative stress and inflammation; however, how redox enzyme concentrations alter in extracellular fluids following bouts of either type of exercise is unknown. Recreationally active men (n = 26, mean ± SD: age 28 ± 8 yr) took part in either: 1) two separate energy-matched cycling bouts: one of moderate intensity (MOD) and a bout of high intensity interval exercise (HIIE) or 2) an eccentric-based resistance exercise protocol (RES). Alterations in plasma (study 1) and serum (study 2) peroxiredoxin (PRDX)-2, PRDX-4, superoxide dismutase-3 (SOD3), thioredoxin (TRX-1), TRX-reductase and interleukin (IL)-6 were assessed before and at various timepoints after exercise. There was a significant increase in SOD3 (+1.5 ng/mL) and PRDX-4 (+5.9 ng/mL) concentration following HIIE only, peaking at 30- and 60-min post-exercise respectively. TRX-R decreased immediately and 60 min following HIIE (-7.3 ng/mL) and MOD (-8.6 ng/mL), respectively. In non-resistance trained men, no significant changes in redox enzyme concentrations were observed up to 48 h following RES, despite significant muscle damage. IL-6 concentration increased in response to all trials, however there was no significant relationship between absolute or exercise-induced changes in redox enzyme concentrations. These results collectively suggest that HIIE, but not MOD or RES increase the extracellular concentration of PRDX-4 and SOD3. Exercise-induced changes in redox enzyme concentrations do not appear to directly relate to systemic changes in IL-6 concentration.NEW & NOTEWORTHY Two studies were conducted to characterize changes in redox enzyme concentrations after single bouts of exercise to investigate the emerging association between extracellular redox enzymes and inflammation. We provide evidence that SOD3 and PRDX-4 concentration increased following high-intensity aerobic but not eccentric-based resistance exercise. Changes were not associated with IL-6. The results provide a platform to investigate the utility of SOD3 and PRDX-4 as biomarkers of oxidative stress following exercise.

The effect of temperature and heat shock protein 72 on the ex vivo acute inflammatory response in monocytes.

The acute inflammatory response to active or passive activities that increase body temperature may aid to reduce chronic low-grade inflammation. This study investigates the impact of temperature and extracellular heat shock protein 72 (eHsp72) on the acute intracellular Hsp72 (iHsp72) and interleukin-6 (iIL-6) response in monocytes. Whole blood was incubated for 2 h at 37.0 °C, 38.5 °C and 40.0 °C, in the absence or presence of 0.5 µg/ml eHsp72. Flow cytometry was used to assess iHsp72 and iIL-6 expression in total monocytes and the three monocyte subsets. Incubation at 40.0 °C (p < 0.001) but not 38.5 °C (p = 0.085) increased iHsp72 expression when compared with 37.0 °C, while there was no effect of temperature on iIL-6 expression (p = 0.635). Following incubation with eHsp72, the expression of iHsp72 in classical monocytes was reduced at all temperatures (p < 0.001), while there was no effect of eHsp72 on iIL-6 expression (p = 0.071). Large temperature elevations are needed to induce an acute iHsp72 response in monocytes. In addition, contrary to its suggested role as a danger signal for the innate immune system, eHsp72 reduced iHsp72 and iIL-6 expression in monocytes.

Anti-inflammatory response to acute exercise is related with intensity and physical fitness.

PURPOSE: The relationship between inflammatory markers and energetic metabolism has been explored. However, the relationship between exercise intensity and fitness status is unclear, and it is necessary to understand this relationship to apply specific exercise guidance. The purpose of the study was to analyze metabolic and inflammatory responses imposed by acute exercise sessions performed at moderate, heavy, and severe intensities and their relationship with the physical fitness status. METHODS: Nineteen healthy male volunteers performed three acute exercise sessions until exhaustion or up to 60 minutes on a cycle ergometer at moderate (90% of first ventilatory threshold [VT1]), heavy (midpoint between VT1 and second ventilatory threshold [VT2]), and severe (midpoint between VT2 and maximal aerobic power) intensities. Blood lactate, glucose, NEFA, endotoxin, and cytokines were determined for each exercise session. Peripheral and lipopolysaccharide (LPS)-stimulated release of tumor necrosis factor alpha (TNF-α), interleukin (IL)-6, and IL-10 was analyzed before, after, and 60 minutes after sessions. RESULTS: In peripheral blood, severe intensity increased lactate, endotoxin, and TNF-α immediately after exercise and glucose at 60 min after exercise. There was a trend for IL-10 increase at 60 minutes after exercise in peripheral blood. Immediately after exercise, LPS-stimulated TNF-α, IL-6, IL-6/IL-10 ratio, and lactate levels were higher in the severe intensity while nonester fatty acid levels decreased at this time. At 60 minute after exercise, higher concentrations of glucose and a trend for increased IL-10 were observed in severe intensity. A positive correlation was observed between maximal aerobic power and IL-10 ( r = 0.513; P = 0.042), and negative correlations between maximal aerobic power and endotoxin ( r = -0.531; P = 0.034) and lactate ( r = -0.538; P = 0.031) in heavy intensity. CONCLUSION: Our data show a novel finding that higher cytokine responses occur at higher intensities, mainly in severe intensity. However, the anti-inflammatory (IL-10) response was physical fitness-dependent.

Regular exercise during haemodialysis promotes an anti-inflammatory leucocyte profile.

BACKGROUND: Cardiovascular disease is the most common cause of mortality in haemodialysis (HD) patients and is highly predicted by markers of chronic inflammation. Regular exercise may have beneficial anti-inflammatory effects, but this is unclear in HD patients. This study assessed the effect of regular intradialytic exercise on soluble inflammatory factors and inflammatory leucocyte phenotypes. METHODS: Twenty-two HD patients from a centre where intradialytic cycling was offered thrice weekly and 16 HD patients receiving usual care volunteered. Exercising patients aimed to cycle for 30 min at rating of perceived exertion of 'somewhat hard'. Baseline characteristics were compared with 16 healthy age-matched individuals. Physical function, soluble inflammatory markers and leucocyte phenotypes were assessed again after 6 months of regular exercise. RESULTS: Patients were less active than their healthy counterparts and had significant elevations in measures of inflammation [interleukin-6 (IL-6), C-reactive protein (CRP), tumour necrosis factor-α (TNF-α), intermediate and non-classical monocytes; all P < 0.001]. Six months of regular intradialytic exercise improved physical function (sit-to-stand 60). After 6 months, the proportion of intermediate monocytes in the exercising patients reduced compared with non-exercisers (7.58 ± 1.68% to 6.38 ± 1.81% versus 6.86 ± 1.45% to 7.88 ± 1.66%; P < 0.01). Numbers (but not proportion) of regulatory T cells decreased in the non-exercising patients only (P < 0.05). Training had no significant effect on circulating IL-6, CRP or TNF-α concentrations. CONCLUSIONS: These findings suggest that regular intradialytic exercise is associated with an anti-inflammatory effect at a circulating cellular level but not in circulating cytokines. This may be protective against the increased risk of cardiovascular disease and mortality that is associated with chronic inflammation and elevated numbers of intermediate monocytes.

Can intervals enhance the inflammatory response and enjoyment in upper-body exercise?

PURPOSE: To investigate the inflammatory and perceptual responses to three different forms of upper-body exercise. METHODS: Twelve recreationally active, able-bodied males performed three work-matched arm-crank sessions in a randomised order: 30 min moderate-intensity continuous (CON), 30 min moderate-intensity with changes in cadence (CAD) and 20 min high-intensity interval training (HIIT). Blood samples were taken pre, post and 2-h post-exercise to determine plasma concentrations of interleukin (IL)-6 and IL-1ra. Perceptual responses pre, during and following the trials were assessed using the Feeling Scale, Felt Arousal Scale, Ratings of Perceived Exertion (RPE) and the Physical Activity Enjoyment Scale (PACES). RESULTS: All trials were evenly effective in inducing an acute inflammatory response, indicated by similar increases in IL-6 after exercise and in IL-1ra at 2-h post exercise for all trials. More negative affect and higher RPE were reported during HIIT compared to CON and CAD, whereas PACES scores reported after exercise were higher for HIIT and CAD compared to CON. CONCLUSIONS: When matched for external work, there was no difference in the inflammatory response to HIIT compared to moderate-intensity upper-body exercise. Although HIIT was (perceived as) more strenuous and affective responses were more negative during this mode, the higher ratings of enjoyment for both HIIT and CAD reported after exercise suggest that the inclusion of variation enhances enjoyment in upper-body exercise. As the fashion in which upper-body exercise is performed does not seem to influence the inflammatory response, it might be advised to prescribe varied exercise to enhance its enjoyment.

Arm and Intensity-Matched Leg Exercise Induce Similar Inflammatory Responses.

INTRODUCTION: The amount of active muscle mass can influence the acute inflammatory response to exercise, associated with reduced risk for chronic disease. This may affect those restricted to upper body exercise, for example, due to injury or disability. The purpose of this study was to compare the inflammatory responses for arm exercise and intensity-matched leg exercise. METHODS: Twelve male individuals performed three 45-min constant load exercise trials after determination of peak oxygen uptake for arm exercise (V˙O2peak A) and cycling (V˙O2peak C): 1) arm cranking exercise at 60% V˙O2peak A, 2) moderate cycling at 60% V˙O2peak C, and 3) easy cycling at 60% V˙O2peak A. Cytokine, adrenaline, and flow cytometric analysis of monocyte subsets were performed before and up to 4 h postexercise. RESULTS: Plasma IL-6 increased from resting concentrations in all trials; however, postexercise concentrations were higher for arm exercise (1.73 ± 1.04 pg·mL) and moderate cycling (1.73 ± 0.95 pg·mL) compared with easy cycling (0.87 ± 0.41 pg·mL; P < 0.04). Similarly, the plasma IL-1ra concentration in the recovery period was higher for arm exercise (325 ± 139 pg·mL) and moderate cycling (316 ± 128 pg·mL) when compared with easy cycling (245 ± 77 pg·mL, P < 0.04). Arm exercise and moderate cycling induced larger increases in monocyte numbers and larger increases of the classical monocyte subset in the recovery period than easy cycling (P < 0.05). The postexercise adrenaline concentration was lowest for easy cycling (P = 0.04). CONCLUSIONS: Arm exercise and cycling at the same relative exercise intensity induces a comparable acute inflammatory response; however, cycling at the same absolute oxygen uptake as arm exercise results in a blunted cytokine, monocyte, and adrenaline response. Relative exercise intensity appears to be more important to the acute inflammatory response than modality, which is of major relevance for populations restricted to upper body exercise.

The effect of prior walking on coronary heart disease risk markers in South Asian and European men.

PURPOSE: Heart disease risk is elevated in South Asians possibly due to impaired postprandial metabolism. Running has been shown to induce greater reductions in postprandial lipaemia in South Asian than European men, but the effect of walking in South Asians is unknown. METHODS: Fifteen South Asian and 14 white European men aged 19-30 years completed two, 2-day trials in a randomised crossover design. On day 1, participants rested (control) or walked for 60 min at approximately 50 % maximum oxygen uptake (exercise). On day 2, participants rested and consumed two high-fat meals over a 9-h period during which 14 venous blood samples were collected. RESULTS: South Asians exhibited higher postprandial triacylglycerol [geometric mean (95 % confidence interval) 2.29 (1.82 to 2.89) vs. 1.54 (1.21 to 1.96) mmol L(-1) h(-1)], glucose [5.49 (5.21 to 5.79) vs. 5.05 (4.78 to 5.33) mmol L(-1) h(-1)], insulin [32.9 (25.7 to 42.1) vs. 18.3 (14.2 to 23.7) µU mL(-1) h(-1)] and interleukin-6 [2.44 (1.61 to 3.67) vs. 1.04 (0.68 to 1.59) pg mL(-1) h(-1)] than Europeans (all ES ≥ 0.72, P ≤ 0.03). Between-group differences in triacylglycerol, glucose and insulin were not significant after controlling for age and percentage body fat. Walking reduced postprandial triacylglycerol [1.79 (1.52 to 2.12) vs. 1.97 (1.67 to 2.33) mmol L(-1) h(-1)] and insulin [21.0 (17.0 to 26.0) vs. 28.7 (23.2 to 35.4) µU mL(-1) h(-1)] (all ES ≥ 0.23. P ≤ 0.01), but group differences were not significant. CONCLUSIONS: Healthy South Asians exhibited impaired postprandial metabolism compared with white Europeans, but these differences were diminished after controlling for potential confounders. The small-moderate reduction in postprandial triacylglycerol and insulin after brisk walking was not different between the ethnicities.

Salivary SIgA responses to acute moderate-vigorous exercise in monophasic oral contraceptive users.

The purpose of this study was to examine the effect of oral contraceptive (OC) use on salivary secretory immunoglobulin A (SIgA) levels at rest and in response to an acute bout of moderate-vigorous exercise during 2 phases of the 4-week OC cycle corresponding to different phases of the synthetic menstrual cycle. Ten healthy active females completed a cycling at 70% peak oxygen uptake for 45 min at 2 time points of an OC cycle: during the equivalent in time to the mid-follicular phase (day 8 ± 2) and the mid-luteal phase (day 20 ± 2). Timed unstimulated saliva samples were obtained before, immediately postexercise, and 1 h postexercise and analyzed for salivary SIgA. Salivary SIgA secretion rate was 26% (95% confidence limits (CI) 6-46) lower at postexercise compared with pre-exercise during the synthetic follicular phase (p = 0.019) but no differences were observed during the synthetic luteal trial. Saliva flow rate was 11% (95% CI, 8-30) lower at postexercise compared with pre-exercise (main effect for time; p = 0.025). In conclusion, the pattern of salivary SIgA secretion rate response to moderate-vigorous exercise varies across the early and late phases of a monophasic OC cycle, with a transient reduction in salivary SIgA responses during the synthetic follicular phase. These findings indicate that monophasic OC use should be considered when assessing mucosal immune responses to acute exercise.