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Sickle cell trait (SCT) is a risk factor of collapse and sudden death in athletes. We conducted a longitudinal study to determine the hematological responses and hydration status in NCAA Division I American football players with SCT. The study took place over 2 years with 6 SCT and 6 position-matched controls (CON) in year 1; and 4 SCT and 4 CON in year 2. In year 2, three of the four SCT players were recruited and re-enrolled with new position-matched controls (total sample data = 10 SCT and 10 CON). Blood samples were taken at three visits: pre-camp, post-camp, and post-season to examine hemoglobin variants, complete blood counts, and chemistry panel 26. Hydration status was assessed by measuring body weight change, urine specific gravity, and urine and sweat electrolyte concentrations during the pre-season training camp. All SCT players were confirmed to have SCT (HbS = 37.9 ± 2.4%) and had greater red cell distribution width (RDW) compared to CON across all visits. Serum uric acid was higher in SCT (7.3 ± 1.0 mg/dL) compared to CON (6.1 ± 0.6 mg/dL; p = 0.001). Furthermore, serum creatine kinase levels were greater in SCT (1617.0 ± 1034.8 IU/L) at pre-camp compared to CON (1037.4 ± 602.8 IU/L; p = 0.03). SCT players exhibited lower pre- and post-practice urine electrolytes and urine specific gravity (SCT pre: 1.019 ± 0.005 vs. CON pre: 1.026 ± 0.008 p

NEW FINDINGS What is the central question of this study? What are the characteristics of the NK cell response following acute moderate-intensity aerobic exercise in prostate cancer survivors and is there a relationship between stress hormones and NK cell mobilization? What is the main finding and its importance? NK cell numbers and proportions changed similarly between prostate cancer survivors and controls following acute exercise. Consecutive training sessions can likely be used without adverse effects on the immune system during prostate cancer treatment. ABSTRACT Prostate cancer treatment affects multiple physiological systems, although the immune response during exercise has been minimally investigated. The objective was to characterize the natural killer (NK) cell response following acute exercise in prostate cancer survivors. Prostate cancer survivors on androgen deprivation therapy (ADT) and those without (PCa) along with non-cancer controls (CON) completed a moderate intensity cycling bout. NK cells were phenotyped before and 0, 2 and 24 h after acute exercise using flow cytometry. CD56 total NK cell frequency increased by 6.2% at 0 h (P

Heart rate variability (HRV) provides a simple method to evaluate autonomic function in health and disease. A reduction in HRV may indicate autonomic dysfunction and is strongly associated with aspects of cardiometabolic disease, including hyperglycemia. Reduced nitric oxide (NO) bioavailability is also implicated in the development of cardiometabolic disease and autonomic dysfunction. Watermelons are natural sources of L-arginine and L-citrulline, substrates used for NO synthesis. Watermelon consumption can improve NO bioavailability. We conducted a randomized, double-blind, placebo-controlled crossover trial to test the effects of 2 weeks of daily watermelon juice (WMJ) supplementation on HRV in response to an oral glucose challenge (OGC) in healthy young adults. We also performed indirect calorimetry to assess if our intervention altered the metabolic response to the OGC. WMJ supplementation preserved high-frequency power (HF) (treatment effect, p = 0.03) and the percentage of successive differences that differ by more than 50 ms (pNN50) (treatment effect, p = 0.009) when compared to the placebo treatment. There was no difference in resting energy expenditure or substate oxidation according to treatment. We report that WMJ supplementation attenuates OGC-induced reductions in HRV. Future work should emphasize the importance of NO bioavailability in autonomic dysfunction in cardiometabolic disease.

Circulating immune cell numbers and phenotypes are impacted by high-intensity acute bouts of exercise and infection history with the latent herpesviruses cytomegalovirus (CMV). In particular, CMV infection history impairs the exercise-induced mobilization of cytotoxic innate lymphoid cells 1 (ILC1) cells, also known as NK cells, in the blood. However, it remains unknown whether exercise and CMV infection modulate the mobilization of traditionally tissue-resident non-cytotoxic ILCs into the peripheral blood compartment. To address this question, 22 healthy individuals with or without CMV (20–35 years—45% CMVpos) completed 30 min of cycling at 70% VO2 max, and detailed phenotypic analysis of circulating ILCs was performed at rest and immediately post-exercise. We show for the first time that a bout of high-intensity exercise is associated with an influx of ILCs that are traditionally regarded as tissue-resident. In addition, this is the first study to highlight that latent CMV infection blunts the exercise-response of total ILCs and progenitor ILCs (ILCPs). These promising data suggest that acute exercise facilitates the circulation of certain ILC subsets, further advocating for the improvements in health seen with exercise by enhancing cellular mobilization and immunosurveillance, while also highlighting the indirect deleterious effects of CMV infection in healthy adults.

There is evidence from human twin and family studies as well as mouse and rat selection experiments that there are considerable interindividual differences in the response of cardiorespiratory fitness (CRF) and other cardiometabolic traits to a given exercise programme dose. We developed this consensus statement on exercise response variability following a symposium dedicated to this topic. There is strong evidence from both animal and human studies that exercise training doses lead to variable responses. A genetic component contributes to exercise training response variability.In this consensus statement, we (1) briefly review the literature on exercise response variability and the various sources of variations in CRF response to an exercise programme, (2) introduce the key research designs and corresponding statistical models with an emphasis on randomised controlled designs with or without multiple pretests and post-tests, crossover designs and repeated measures designs, (3) discuss advantages and disadvantages of multiple methods of categorising exercise response levels—a topic that is of particular interest for personalised exercise medicine and (4) outline approaches that may identify determinants and modifiers of CRF exercise response. We also summarise gaps in knowledge and recommend future research to better understand exercise response variability.

Long-duration spaceflights reportedly induce immune dysregulation, which is considered a risk to astronaut safety and mission success. Recent studies have examined the impact of spaceflight on markers of adaptive and innate immunity, but no study, to date, has comprehensively evaluated humoral immunity and serological markers of B cell function. The aim of this study was to characterize changes in B cell numbers and phenotypes, along with plasma Igs and polyclonal free light chains (FLCs)—near-“real-time” biomarkers of Ig synthesis—in response to an ~6-mo mission to the International Space Station (ISS). Whole-blood samples were collected before flight, during flight (“Early flight,” “Mid-flight,” and “Late flight”), immediately upon return, and during a recovery period (R + 18, R + 30/R + 33, and R + 60/R + 66) from 23 ISS crew members. B Cell counts and phenotypes were measured throughout the duration of the mission, along with total plasma Ig and FLC levels. There was no effect of spaceflight on the number and proportion of the different B cell subsets. There was no difference in kappa FLC between preflight samples and either in-flight or recovery samples ( P > 0.05), and only a marginal reduction was observed in lambda FLC levels upon return to Earth ( P < 0.05). Furthermore, IgG and IgM remained unchanged during and after spaceflight compared with preflight values ( P > 0.05). Of note, plasma IgA concentrations were elevated in-flight compared with baseline and recovery values ( P < 0.05). These results indicate that B cell homeostasis is maintained during long-duration spaceflight, advocating for potential in-flight vaccination as viable countermeasures against viral reactivation during exploration-class missions.

BACKGROUND: Acute hyperglycemia reduces NO bioavailability and causes macro- and microvascular dysfunction. Watermelon juice (WMJ) is a natural source of the amino acid citrulline, which is metabolized to form arginine for the NO cycle and may improve vascular function. OBJECTIVES: We examined the effects of 2 weeks of WMJ compared to a calorie-matched placebo (PLA) to attenuate acute hyperglycemia-induced vascular dysfunction. METHODS: In a randomized, placebo-controlled, double-blind, crossover trial, 6 men and 11 women (aged 21–25; BMI, 23.5 ± 3.2 kg/m(2)) received 2 weeks of daily WMJ (500 mL) or a PLA drink followed by an oral-glucose-tolerance test. Postprandial flow-mediated dilation (FMD) was measured by ultrasound (primary outcome), while postprandial microvascular blood flow (MVBF) and ischemic reperfusion were measured by near-infrared spectroscopy (NIRS) vascular occlusion test (VOT). RESULTS: The postprandial FMD area AUC was higher after WMJ supplementation compared to PLA supplementation (838 ± 459% · 90 min compared with 539 ± 278% · 90 min; P = 0.03). The postprandial MVBF (AUC) was higher (P = 0.01) following WMJ supplementation (51.0 ± 29.1 mL blood · 100 mL tissue(–1) · min(–1) · 90 min) compared to the PLA (36.0 ± 20.5 mL blood · 100 mL tissue(–1) · min(–1) · 90 min; P = 0.01). There was a significant treatment effect (P = 0.048) for WMJ supplementation (71.2 ± 1.5%) to increase baseline tissue oxygen saturation (StO(2)%) when compared to PLA (65.9 ± 1.7%). The ischemic-reperfusion slope was not affected by WMJ treatment (P = 0.83). CONCLUSIONS: Two weeks of daily WMJ supplementation improved FMD and some aspects of microvascular function (NIRS-VOT) during experimentally induced acute hyperglycemia in healthy adults. Preserved postprandial endothelial function and enhanced skeletal muscle StO(2)% are likely partially mediated by increased NO production (via citrulline conversion into arginine) and by the potential antioxidant effect of other bioactive compounds in WMJ.

Long duration spaceflights are associated with profound dysregulation of the immune system and latent viral reactivations. However, little is known on the impact of long duration spaceflight on innate immunity which raises concerns on crewmembers' ability to fight infections during a mission. The aim of this study was to determine the effects of spaceflight on plasma antimicrobial proteins (AMPs) and how these changes impact latent herpesvirus reactivations. Plasma, saliva and urine samples were obtained from 23 crewmembers before, during and after a 6-month mission on the International Space Station (ISS). Plasma AMP concentrations were determined by ELISA, and saliva Epstein-Barr virus (EBV) and varicella zoster virus (VZV) and urine cytomegalovirus (CMV) DNA levels were quantified by Real-Time PCR. There was a non-significant increase in plasma HNP1-3 and LL-37 during the early and middle stages of the missions, which was significantly associated with changes in viral DNA during and after spaceflight. Plasma HNP1-3 and Lysozyme increased at the late mission stages in astronauts who had exhibited EBV and VZV reactivations during the early flight stages. Following return to Earth and during recovery, HNP1-3 and lysozyme concentrations were associated with EBV and VZV viral DNA levels, reducing the magnitude of viral reactivation. Reductions in plasma LL-37 upon return were associated with greater CMV reactivation. This study shows that biomarkers of innate immunity appeared to be partially restored after 6-months in space and suggests that following adaptation to the space environment, plasma HNP1-3 and lysozyme facilitate the control of EBV and VZV reactivation rate and magnitude in space and upon return on earth. However, the landing-associated decline in plasma LL-37 may enhance the rate of CMV reactivation in astronauts following spaceflight, potentially compromising crewmember health after landing.

As the international space community plans for manned missions to Mars, spaceflight-associated immune dysregulation has been identified as a potential risk to the health and safety of the flight crew. There is a need to determine whether salivary antimicrobial proteins, which act as a first line of innate immune defense against multiple pathogens, are altered in response to long-duration (>6 mo) missions. We collected 7 consecutive days of whole and sublingual saliva samples from eight International Space Station (ISS) crewmembers and seven ground-based control subjects at nine mission time points, ~180 and ~60 days before launch (L−180/L−60), on orbit at flight days ~10 and ~90 (FD10/FD90) and ~1 day before return (R−1), and at R+0, R+18, R+33, and R+66 days after returning to Earth. We found that salivary secretory (s)IgA, lysozyme, LL-37, and the cortisol-to-dehydroepiandrosterone ratio were elevated in the ISS crew before (L−180) and during (FD10/FD90) the mission. “Rookie” crewmembers embarking on their first spaceflight mission had lower levels of salivary sIgA but increased levels of α-amylase, lysozyme, and LL-37 during and after the mission compared with the “veteran” crew who had previously flown. Latent herpesvirus reactivation was distinct to the ~6-mo mission crewmembers who performed extravehicular activity (“spacewalks”). Crewmembers who shed at least one latent virus had higher cortisol levels than those who did not shed. We conclude that long-duration spaceflight alters the concentration and/or secretion of several antimicrobial proteins in saliva, some of which are related to crewmember flight experience, biomarkers of stress, and latent viral reactivation. NEW & NOTEWORTHY Spaceflight-associated immune dysregulation may jeopardize future exploration-class missions. Salivary antimicrobial proteins act as a first line of innate immune defense. We report here that several of these proteins are elevated in astronauts during an International Space Station mission, particularly in those embarking on their first space voyage. Astronauts who shed a latent herpesvirus also had higher concentrations of salivary cortisol compared with those who did not shed. Stress-relieving countermeasures are needed to preserve immunity and prevent viral reactivation during prolonged voyages into deep space.

Collegiate athletes are exposed to varying levels of academic and physical stressors, placing them at increased risk for stress-activated latent viral infections. However, the impact of allostatic stress load on the immune response to maximal exercise in athletes remains largely unknown. This study examined the effects of a 7-mo training period and cytomegalovirus (CMV) serostatus on immune cell response to high-intensity swim tests within a group of collegiate swimmers. Samples were collected from 15 National Collegiate Athletic Association Division I swimmers (9 men, 6 women: 19.87 ± 0.64 yr) before and after exhaustive in-pool swims at 2 time points (V1: immediately post-season 1 and V3: beginning of season 2). An additional off-season (V2) time point was collected in a subset of 9 swimmers. Natural killer (NK) cell, B cell, and T cells were quantified by flow cytometry. Linear mixed models were used to determine the effects of exercise, time point, and CMV serostatus (α = 0.05). Resting senescent CD8+ T cells were higher in CMV-seropositive participants at V3 ( P = 0.005). CMV-seronegative participants had a decrease in resting senescent CD8+ T cells from V1 to V3 ( P = 0.021). After acute exercise, CMV-seropositive participants had lower naïve CD8+ T cells ( P < 0.001) and higher senescent CD8+ T cells ( P < 0.001). Increased cumulative stress levels did not appear to affect B-cell and NK-cell compartments. Immune response to exercise was impacted by CMV serostatus and allostatic stress load. Young CMV-seropositive athletes exposed to elevated stressors should be monitored to determine long-term effects of training and academic stressors. NEW & NOTEWORTHY Allostatic stress load is associated with impaired immune response to maximal exercise in cytomegalovirus (CMV)-seropositive subjects but not in CMV-seronegative young healthy adults.

We assessed metabolic flexibility (MF) via a mixed meal in a group of young, healthy participants with a positive family history of maternal type 2 diabetes (T2D) (FH+) and those without a family history of T2D (FH−) under three distinct conditions; baseline (BL; no previous exercise), 1‐h post high intensity interval exercise (1H), and 48‐h post exercise recovery. On separate visits, participants completed a single bout of high intensity interval exercise (HIIE) and repeated the MMTT 1‐h (1H) and 48 h (48H) postexercise. FH+ participants were not able to suppress fat oxidation 1‐h post exercise (1H) as effectively as FH− participants were, however, this response was improved when measured at the 48H visit. Insulin AUC was significantly lowered at both 1H and 48H when compared to the BL visit. Serum NEFA AUC was elevated 1‐h post exercise, when compared to BL, but was significantly reduced at the 48H visit. Young, healthy participants with a maternal history of T2D demonstrate impaired MF (related to the inability to suppress fat oxidation) in response to acute HIIE (1H) that was improved 48H. The overall effect of HIIE showed improved insulin AUC and NEFA AUC up to 48H post that did not differ by FH.

Background: Targeting mitochondrial function has regained traction as a viable anti-cancer strategy. Here, we characterized the phenotypic and transcriptomic landscape of human triple negative breast cancer (TNBC) cells following exposure to the mitochondrial uncoupler BAM15. Methods: Cell viability and IC50 were determined by MTS assay after treatment (24-hours) with doxorubicin, cyclophosphamide, or BAM15 (0-100 µM). Mitochondrial membrane potential (ΔΨm) was measured by TMRM staining in live (Annexin V negative) cells using flow cytometry after acute (15-minutes) and chronic (16-hours) exposure to BAM15. Untargeted RNA sequencing was conducted after chronic (16-hours) exposure to BAM15 (1, 10, and 20 µM). Differentially expressed genes were determined by using DESeq2 package in R with the following cutoffs: false discovery rate 1.5. Pathway enrichment analysis was then used to identify canonical signaling networks and upstream regulators and specific gene targets were validated by real-time qPCR. Results: BAM15 reduced cell viability with an IC50 similar to doxorubicin and superior to cyclophosphamide. Acute exposure to BAM15 reduced ΔΨm by ~60% which saturated at 1 µM. After 16-hour exposure to BAM15, ΔΨm recovered at 1 µM, but was reduced by ~40% at 10 and 20 µM conditions. Through untargeted sequencing, we identified 2108 transcripts that were differentially regulated by BAM15 (20 µM vs. vehicle), 968 of which were upregulated and 1140 downregulated. To contextualize these findings, we performed pathway enrichment analysis on genes differentially expressed by BAM15. Canonical signaling pathways related cell survival, proliferation, energy production, and DNA damage were differentially regulated by BAM15. A number of known transcriptional factors required for cell division, replication, and survival, including CCNE2, E2F1, CDC6, CDC20, MCM3, MCM6, AURKA, UBEC2C, and S100A4, were inhibited by BAM15. Notably, genes and pathways essential to ATP production, including both glycolysis and oxidative phosphorylation, were dramatically reduced by BAM15, including LDHA and MT-CO1. Conclusions: Taken together, these findings reveal transcriptomic signatures and canonical signaling pathways that mediate the pro-apoptotic and anti-proliferative effects of sustained mitochondrial uncoupling. Citation Format: Elizabeth R. Zunica, Christopher L. Axelrod, Eunhan Cho, Guillaume Spielmann, Shengping Yang, L Anne Gilmore, John P. Kirwan. Untargeted sequencing of human breast cancer reveals induction of pro-apoptotic and anti-proliferative transcriptional signatures in response to mitochondrial uncoupling [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2145.

Purpose: Obesity is an independent risk factor for the development, morbidity, and mortality of breast cancer. Calorie restriction (CR) is the first line therapy for obesity management, with growing evidence and application in the treatment of breast cancer. In non-tumor bearing patients, ~20% of weight loss is attributed to reductions in skeletal muscle mass. However, little is known of how CR in a tumorigenic environment may influence muscle function and content. Methods: Obese C57BL/6J female mice were used to develop an allograft breast cancer model by orthotopically injecting the mammary fat pad with basal-like breast cancer (E0771 cells). Mice were randomized (1:1) by tumor size and body weight to high fat diet (HFD; 60% kcal from fat) or calorie restriction diet (CRD; ~40% restriction of HFD via an incremental reduction in food intake) for 2.5 weeks. Daily food intake, body weight and temperature, as well as twice weekly tumor measurements were obtained during treatment. Organ weights and size were obtained at the time of necropsy. Whole blood was collected for immunophenotyping and assessed via flow cytometry. Mitochondrial function was determined in tumor homogenates and permeabilized gastrocnemius fibers by high resolution respirometry (O2k). Results: CRD reduced body weight (HFD: 27.8±0.8 vs CRD: 22.9±0.5 g, P=0.0003) and tumor growth (HFD: 3.6±0.2 g vs. CRD: 2.7±0.3 g, P=0.03). There was no difference in the proportions of total NK cells, helper and cytotoxic T-cells between HFD and CRD (P>0.05). Respirometry studies of tumor mitochondria revealed diminished complex I uncoupled rate following CRD (HFD: 3.2±0.4 vs. CRD: 1.6±0.3 pmol/sec/mg, P= 0.02). Additionally, skeletal muscle mitochondria of CRD animals contained a defect in complex I oxidation (HFD: 49.2±6.5 vs. CRD: 28.6±4.0 pmol/sec/mg, P=0.03). Furthermore, soleus muscle mass was reduced (HFD: 7.7±0.8 mg vs. CRD: 4.5±1.1 mg, P=0.04). Conclusions: This study demonstrates that CRD induces complex I (CI) defects in tumor and skeletal muscle mitochondria. Suppression of CI was associated with a favorable reduction in tumor growth and unfavorable loss of skeletal muscle mass. Future studies formally evaluating skeletal muscle function and cachexia as well as muscle preserving therapies in combination with CR are warranted. Funding: Research was supported by NIGMS (GM104940 - JPK) and the Pennington Biomedical Research Foundation (LAG) Citation Format: Elizabeth R. Zunica, Christopher L. Axelrod, Gangarao Davuluri, Wagner S. Dantas, Guillaume Spielmann, Eunhan Cho, Brian A. Irving, John P. Kirwan, L. Anne Gilmore. Calorie restriction induces skeletal muscle wasting and a complex I defect while reducing mammary tumor growth in a mouse model of diet induced obesity [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4796.

Maintaining astronaut health during space travel is paramount for further human exploration of the solar system beyond Earth’s orbit. Of concern are potential dysregulations in immunity, which could increase the likelihood of cancer and latent viral reactivation. Natural killer (NK) cells are critical effectors of the innate immune system, and their function and phenotype are important to immunosurveillance of nascent tumors and latent viral infections. We compared changes in NK cell phenotype and function in eight crew members who completed an ~6-mo mission to the International Space Station (ISS) with healthy controls who remained on Earth. Assessments were made before (180 and 60 days before launch), during [flight day + 90 days (FD+90) and 1 day before return (R−1)], and after the mission (at R+0, R+18, R+33, and R+66). These samples, plus an additional in-flight sample (FD+180), were collected from a crew member who spent 340 days (~1 yr) on the ISS. NK cell cytotoxic activity (NKCA) against K562 leukemia targets in vitro was reduced by ~50% at FD+90 in ISS crew but not controls. This decrease was more pronounced in “rookie” compared with “veteran” crew members. The ~1-yr mission crew member did not show declines in NKCA against K562 until late in the mission (R−1 and R+0). NK cell numbers, expression of activating and inhibitory receptors, target cell binding, and expression and degranulation of perforin and granzyme B were unaltered with spaceflight. Similarly, when we exposed an immortalized NK cell line (NK-92) to sera collected at different mission time points (before, during, and after flight), there was no effect on NKCA. This is the first study to report impaired NK cell function during long-duration space travel. Countermeasures may be needed to mitigate immune system impairment in exploration class mission crew during long-duration spaceflight missions. NEW & NOTEWORTHY Immune system impairment may inhibit future human space exploration missions to Mars. Natural killer (NK) cells are key components of immunity and vital for tumor surveillance and the prevention of latent virus reactivation. We report that NK cell function is impaired in astronauts during an ~6-mo orbital space mission compared with preflight levels and ground-based controls. Declines in NK cell function were more marked in first-time “rookie” fliers. Countermeasures are needed to preserve NK cell-mediated immunity during spaceflight.

Background: Rheumatoid arthritis (RA) is a chronic inflammatory disease in which adults have significant joint issues leading to poor health. Poor health is compounded by many factors, including exercise avoidance and increased risk of opportunistic infection. Exercise training can improve the health of patients with RA and potentially improve immune function; however, information on the effects of high-intensity interval training (HIIT) in RA is limited. We sought to determine whether 10 weeks of a walking-based HIIT program would be associated with health improvements as measured by disease activity and aerobic fitness. Further, we assessed whether HIIT was associated with improved immune function, specifically antimicrobial/bacterial functions of neutrophils and monocytes.Methods: Twelve physically inactive adults aged 64 ± 7 years with either seropositive or radiographically proven (bone erosions) RA completed 10 weeks of high-intensity interval walking. Training consisted of 3 × 30-minute sessions/week of ten ≥ 60-second intervals of high intensity (80–90% VO2reserve) separated by similar bouts of lower-intensity intervals (50–60% VO2reserve). Pre- and postintervention assessments included aerobic and physical function; disease activity as measured by Disease Activity score in 28 joints (DAS28), self-perceived health, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR); plasma interleukin (IL)-1β, IL-6, chemokine (C-X-C motif) ligand (CXCL)-8, IL-10, and tumor necrosis factor (TNF)-α concentrations; and neutrophil and monocyte phenotypes and functions.Results: Despite minimal body composition change, cardiorespiratory fitness increased by 9% (change in both relative and absolute aerobic capacity; p p p = 0.001) with significant reductions in ESR and swollen joints as well as improved self-perceived health. Neutrophil migration toward CXCL-8 (p = 0.003), phagocytosis of Escherichia coli (p = 0.03), and ROS production (p +)/CD16+ monocytes was reduced (p = 0.002), with both nonclassical (CD14dim/CD16bright) and intermediate (CD14bright/CD16positive) monocytes being reduced (both p p E. coli increased (p = 0.02). No changes were observed for inflammatory markers IL-1β, IL-6, CXCL-8, IL-10, CRP, or TNF-α.Conclusions: We report for the first time, to our knowledge, that a high-intensity interval walking protocol in older adults with stable RA is associated with reduced disease activity, improved cardiovascular fitness, and improved innate immune functions, indicative of reduced infection risk and inflammatory potential. Importantly, the exercise program was well tolerated by these patients.Trial registration: ClinicalTrials.gov, NCT02528344. Registered on 19 August 2015.

Salivary antimicrobial proteins (sAMPs) protect the upper respiratory tract (URTI) from invading microorganisms and have been linked with URTI infection risk in athletes. While high training volume is associated with increased URTI risk, it is not known if fitness affects the sAMP response to acute exercise. This study compared the sAMP responses to various exercising workloads of highly fit experienced cyclists with those who were less fit. Seventeen experienced cyclists (nine highly fit; eight less fit) completed three 30-min exercise trials at workloads corresponding to −5, +5 and +15 % of the individual blood lactate threshold. Saliva samples were collected pre- and post-exercise to determine the concentration and secretion of α-amylase, human neutrophil proteins 1–3 (HNP1–3) lactoferrin, LL-37, lysozyme, and salivary SIgA. The concentration and/or secretion of all sAMPs increased post-exercise, but only α-amylase was sensitive to exercise workload. Highly fit cyclists had lower baseline concentrations of α-amylase, HNP1–3, and lactoferrin, although secretion rates did not differ between the groups. Highly fit cyclists did, however, exhibit greater post-exercise increases in the concentration and/or secretion of a majority of measured sAMPs (percentage difference between highly fit and less fit in parentheses), including α-amylase concentration (+107 %) and secretion (+148 %), HNP1–3 concentration (+97 %) and secretion (+158 %), salivary SIgA concentration (+181 %), lactoferrin secretion (+209 %) and LL-37 secretion (+138 %). We show for the first time that fitness level is a major determinant of exercise-induced changes in sAMPs. This might be due to training-induced alterations in parasympathetic and sympathetic nervous system activation.

The redeployment of NK-cells in response to an acute bout of exercise is thought to be an integral component of the “fight-or-flight” response, preparing the body for potential injury or infection. We showed previously that CMV seropositivity impairs the redeployment of NK-cells with exercise in the young. In the current study, we examined the effect of aging on the redeployment of NK-cells with exercise in the context of CMV. We show here that CMV blunts the exercise-induced redeployment of NK-cells in both younger (23–39 yrs) and older (50–64 yrs) subjects with olderCMVnegsubjects showing the largest postexercise mobilization and 1 h postexercise egress of NK-cells. The blunted exercise response inCMVposindividuals was associated with a decreased relative redeployment of the CD158a+ and CD57+ NK-cell subsets in younger and older individuals. In addition, we show that aging is associated with a CMV-independent increase in the proportion of NK-cells expressing the terminal differentiation marker CD57, while CMV is associated with an age-dependent decrease in the proportion of NK-cells expressing the inhibitory receptors KLRG1 (in the younger group) and CD158a (in the older group). Collectively, these data suggest that CMV may decrease NK-cell mediated immunosurveillance after exercise in both younger and older individuals.