AIM:Indoles are tryptophan (Trp)-derived metabolites that are produced by the gut microbiota and may influence the gut-microbiota-brain axis in multiple sclerosis (MS). Indole-3-lactate (ILA) is reduced in persons with MS and improves MS clinical scores in animal models via its anti-inflammatory remyelinating properties. The ILA/indole-3-acetate (IAA) (ILA/AA) index is considered a neuroprotection index. Physical exercise and diet can modify gut microbiota and indole metabolism. METHODS:This secondary analysis of a randomized control trial aimed to assess the effects of acute and chronic exercise on serum indoles in relapsing-remitting MS (RRMS). Thirty-one RRMS patients (≥ 70% session attendance) completed a 10 week multimodal functional training (60 min, 3×/week) vs. a waitlist control group. Blood samples were collected at baseline and compared to a matched healthy control group, and after 10 weeks for the assessment of chronic effects. Additionally, acute effects of a single bout of exercise were assessed with a blood sample before, during, and immediately after one interim training session. Serum indole concentrations were measured using LC-MS/MS. RESULTS:Baseline indole levels in RRMS patients differed from those of matched healthy controls, and reduced ILA levels were observed. The 10 week intervention increased the ILA/IAA index, while a single exercise bout induced an increase in both ILA and ILA/IAA. CONCLUSION:Multimodal functional training over 10 weeks led to an improved ILA/IAA index suggesting a neuroprotective shift in gut microbiota composition, and a single bout acutely increases the circulating level of ILA. STUDY REGISTRATION NUMBER:DRKS00017091.

The positive effect of exercise on the immune system is widely acknowledged, but the molecular response of immune cells to exercise remains largely unknown. Here, we perform mass-spectrometry-based proteomic analysis on peripheral blood mononuclear cells (PBMC) at a depth of >6000 proteins. Comparing high-intensity interval exercise (HIIE) and moderate-intensity continuous exercise (MICE), matched for time and workload, we identify versatile changes in the proteomic makeup of PBMCs and reveal profound alterations, related to effector function and immune cell activation pathways within one hour following exercise. These changes are more pronounced after HIIE compared to MICE and occur despite identical immune cell mobilization patterns between the two exercise conditions. We further identify an immunoproteomic signature that effectively predicts cardiorespiratory fitness, thus allowing insights into potential exercise-triggered adaptations and immunological health benefits that are mediated by exercise. This study provides a reliable data resource that expands our knowledge on how exercise modulates the immune system, and delivers biological evidence supporting the WHO 2020 guidelines, which highlight exercise intensity as a relevant factor to maintain health.

Impulsivity, a personality construct linked to various psychiatric disorders, is partially regulated by serotonergic neurotransmission. While genetic polymorphisms affecting serotonin transporter (5-HTT) transcription have been widely studied, the role of epigenetic modifications, particularly DNA methylation, remains unclear. Building on earlier analyses from the present cohort that demonstrated that eight weeks of physical exercise reduces impulsivity, this study investigated whether these behavioural changes are accompanied by alterations in 5-HTT expression together with 5-HTT and MAO-A promoter methylation in buffy coat (BC) cells. drks.de, TRN: DRKS00016589, Registration date: 6 February 2019. Participants (n = 45) were randomly assigned to either high-intensity interval training (HIIT) or stretching (active control). Each group completed three training sessions per week for eight weeks, with pre- and post-intervention assessments of impulsivity, 5-HTT gene expression, and 5-HTT and MAO-A promoter methylation. Results indicate a significant increase in 5-HTT expression in the HIIT group compared to controls (p = .008, ηp² = 0.156; d = 0.782), but no corresponding changes in promoter DNA methylation. Moreover, changes in 5-HTT expression did not correlate with changes in impulsivity. Specific 5-HTT and MAO-A promoter methylation changes were weakly associated with certain impulsivity factors. These findings suggest that exercise influences serotonergic function by increasing 5-HTT expression independently of promoter DNA methylation changes. Further research is needed to determine whether these changes are also present at central nervous system level or if this upregulation is primarily a result of long-term anti-inflammatory effects triggered by physical exercise.

Nicotinamide adenine dinucleotide (NAD+) coenzymes are the central electron carriers in biological energy metabolism. Low NAD+ levels are proposed as a hallmark of ageing and several diseases, which has given rise to therapeutic strategies that aim to tackle these conditions by boosting NAD+ levels. As a lifestyle factor with preventive and therapeutic effects, exercise increases NAD+ levels across various tissues, but so far human trials are mostly focused on skeletal muscle. Given that immune cells are mobilized and redistributed in response to acute exercise, we conducted two complementary trials to test the hypothesis that a single exercise session alters NAD+ metabolism of peripheral blood mononuclear cells (PBMCs). In a randomized crossover trial (DRKS00017686) with 24 young adults (12 female) we show that acute exercise increases gene expression and protein abundance of several key NAD+ metabolism enzymes with high conformity between high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT). In a longitudinal exercise trial (DRKS00029105) with 12 young adults (6 female) we confirm these results and reveal that - similar to skeletal muscle - NAD+ salvage is pivotal for PBMCs in response to exercise. Nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme of NAD+ salvage pathway, displayed a pronounced increase in gene expression during exercise, which was accompanied by elevated intracellular NAD+ levels and reduced serum levels of the NAD+ precursor nicotinamide. These results demonstrate that acute exercise triggers NAD+ biosynthesis of human PBMCs with potential implications for immunometabolism, immune effector function, and immunological exercise adaptions.

AIM:Recent pre-clinical evidence suggests that the tryptophan metabolite 3-hydroxyanthranilic acid (3-HAA) and the related enzyme activity along the kynurenine metabolic pathway (KP) are associated with lifespan extension. We aimed to translate these findings into humans and expose exercise training as a potential non-pharmacological intervention to modulate this metabolic hub. METHODS:To explore whether recent pre-clinical findings might also be of relevance for humans, we analyzed the evolutionary conservation of KYNU and HAAO, the two core KP enzymes associated with 3-HAA. In a cross-sectional analysis of young-to-middle-aged adults (N = 84), we examined potential associations of serum 3-HAA and its precursor anthranilic acid with age. We then investigated whether 26 weeks of endurance exercise (increasing intensity (INC) during the intervention period (n = 17) vs. conventional moderate continuous training (CON) matched for energy expenditure (n = 17)) impacted 3-HAA levels, related metabolic ratios, and other KP metabolites. RESULTS:We demonstrate that the core KP enzymes associated with 3-HAA are evolutionarily conserved in humans. Serum 3-HAA and its precursor anthranilic acid were consistently associated with age in young-to-middle-aged adults. Both exercise modes tested induced an increase in 3-HAA levels of 134% (p < 0.001) and 85% (p < 0.001) compared with baseline, respectively, without a significant time*group interaction effect. CONCLUSION:We translate the association between systemic 3-HAA levels and age from animal models into humans and highlight longer-term exercise training as an efficient strategy to boost systemic 3-HAA levels in middle-aged adults. Our findings open promising research avenues concerning the mediating role of 3-HAA in training adaptations, health, and longevity.

BACKGROUND:The biological foundation of changes in mental state after acute exercise is not yet understood, but it may be related to immunological alterations. The study investigated the hypothesis that the exercise-induced mobilization in circulating immune cells and cellular inflammation markers are associated with changes in the subjective mental state. As a secondary aim, the study investigated, wether the effects of the circulating immune cells are sex-dependent. METHODS:In a randomized cross-over trial, 24 young healthy adults (eight female; age 25.75 ± 4.35 years) completed a single exercise bout until exhaustion on a cycle ergometer and a passive control session. Outcomes were assessed immediately before, after the session, and 1 h, 3 h, 24 h, and 48 h after the session and comprise cell counts of leukocytes, lymphocytes, neutrophils and platelets, and the inflammation markers neutrophil-to-lymphocyte-ratio, platelet-to-lymphocyte-ratio and systemic-immune-inflammation-index as blood-based parameters, and subjective mental state measured using the Multidimensional-Mood-Questionnaire (MDMQ, subdomains mood, energetic arousal, calmness). RESULTS:There were significant time*group effects for all blood-based parameters (p < 0.001) and significant main effects of time for the MDMQ mood (p < 0.001) and energetic arousal (p = 0.008). No significant sex-dependent differences were obeserved. Within the intervention group, MDMQ energetic arousal showed significant correlations with lymphocytes (rrm=-0.41, p < 0.001), platelets (rrm=-0.28, p = 0.002), NLR (rrm=0.28, p = 0.002), PLR (rrm=0.33, p < 0.001), SII (rrm=0.269, p = 0.003) and MDMQ calmness showed significant correlations with leukocytes (rrm=-0.29, p = 0.002), lymphocytes (rrm=-0.36, p < 0.001), platelets (rrm=-0.30, p = 0.001), and PLR (rrm=0.25, p = 0.007). Within the control group, MDMQ mood showed significant correlations with lymphocytes (rrm=0.20, p = 0.031, NLR (rrm=-0.28, p = 0.002), PLR (rrm=-0.19, p = 0.033), SII (rrm=-0.24, p = 0.008) and MDMQ calmness showed significant correlations with PLR (rrm=-0.23, p = 0.011), SII (rrm=-0.20, p = 0.029). Fisher´s z-test revealed no significant difference between the correlations of the groups. CONCLUSION:Acute exhaustive exercise affects immune cells, inflammation markers, and the subjective mental state regardless of sex. The correlation between blood-based parameters and the MDMQ appears to be robust and indicates relevant psychoneuroimmune associations in the human body. However, the acute exercise intervention used in this study does not influence this association. CLINICAL TRIAL REGISTRATION NUMBER:DRKS00028792.

Exercise-driven alterations of the immune system are a key mechanism in the prevention and treatment of various diseases. Here, we performed mass spectrometry-based proteomics analysis on peripheral blood mononuclear cells (PBMCs) at a depth of >6000 proteins. Comparing time- and workload-matched high-intensity interval exercise (HIIE) and moderate-intensity continuous exercise (MICE) we discover versatile changes in the proteomic makeup of PBMCs and reveal profound alterations related to effector function and immune cell activation pathways within one hour after exercise. These changes were more pronounced after HIIE compared to MICE and occurred despite identical immune cell mobilization patterns between the two exercise conditions. We further identify an immunoproteomic signature that effectively predicts cardiorespiratory fitness. This study provides a reliable data resource that expands our knowledge on how exercise modulates the immune system, and delivers biological evidence supporting the WHO 2020 guidelines, which highlight exercise intensity as a relevant factor to maintain health. ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Trial DRKS00017686 ### Funding Statement This study received internal funding by the German Sport University Cologne. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethics committee/IRB of the German Sport University Cologne gave ethical approval for this work. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present work are contained in the manuscript or available online.

Background: Multiple Sclerosis (MS) represents a neuroinflammatory autoimmune disease characterized by the predominance of circulating T cell subsets with proinflammatory characteristics and increased central nervous system (CNS)-homing potential. Substantial evidence confirms various beneficial effects of chronic exercise interventions in MS, but it is unknown how long-term multi-modal intense exercise affects MS-associated lymphocytes that are commonly targeted by medication in persons with relapsing remitting MS (pwRRMS). Methods: A total of 45 participants with defined RRMS were randomized to either the exercise (n = 22) or passive waitlist-control group (n = 23). A 10-week intervention consisting of progressive resistance and strength-endurance exercises was applied (3x/week & agrave; 60 min). Blood was drawn before (T-1) and after (T-2) the intervention period. Flow cytometry was used for phenotyping lymphocyte subsets. Results: Relative protein expression of CD49d within CD8(+) T cells, quantified via mean fluorescence intensity (MFI), is significantly associated with the Expanded Disability Status Scale (p = 0.007, r = 0.440), decreased in the exercise group (p = 0.001) only, and was significantly lower in the exercise compared to the control group at T-2 (p < 0.001). T helper (Th) 17 cell frequency decreased only in the exercise group (p < 0.001). CD8(+)CD20(+) T cell frequency was significantly lower in the exercise compared to the control group at T-2 (p = 0.003), without showing significant time effects. Conclusion: The 10-week multimodal exercise intervention mainly affected circulating T cells harboring a pathophysiological phenotype in MS. The findings of a decreased frequency of pathogenic Th17 cells and the reduced CNS-homing potential of CD8(+) T cells, indicated by reduced CD49d MFI, substantiate the positive effects of exercise on cellular biomarkers involved in disease activity and progression in MS. To confirm exercise-mediated beneficial effects on both disease domains, clinical endpoints (i.e., relapse rate, lesion formation, EDSS score) should be assessed together with these cellular and molecular markers in studies with a larger sample size and a duration of six to twelve months or longer.

BACKGROUND:B cells represent a crucial component of adaptive immunity that ensures long-term protection from infection by generating pathogen-specific immunoglobulins. Exercise alters B cell counts and immunoglobulin levels, but evidence-based conclusions on potential benefits for adaptive immunity are lacking. This systematic review assessed current literatures on the impact of acute exercise and exercise training on B cells, immunoglobulins, and markers of secretory immunity in human biofluids.METHODS:According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, MEDLINE, Web of Science, and Embase were searched on March 8, 2023. Non-randomized controlled trials and crossover trials investigating the impact of acute exercise or exercise training on B cell counts and proportions, immunoglobulin levels, salivary flow rate, or secretory immunoglobulin A secretion rate were included. Quality and reporting of exercise training studies were assessed using the Tool for the Assessment of Study Quality and reporting in Exercise. Study characteristics, outcome measures, and statistically significant changes were summarized tabularly.RESULTS:Of the 67 eligible studies, 22 applied acute exercise and 45 applied exercise training. All included outcomes revealed significant alterations over time in acute exercise and exercise training context, but only a few investigations showed significant differences compared to control conditions. Secretory and plasma immunoglobulin A levels were most consistently increased in response to exercise training.CONCLUSION:B cell-related outcomes are altered by acute exercise and exercise training, but evidence-based conclusions cannot be drawn with high confidence due to the large heterogeneity in populations and exercise modalities. Well-designed trials with large sample sizes are needed to clarify how exercise shapes B cell-related immunity.

The kynurenine pathway of tryptophan degradation generates several metabolites such as kynurenine or kynurenic acid that serve as endogenous ligands of the aryl hydrocarbon receptor (AHR). Due to its distinct biological roles particularly modulating the immune system, the AHR is a current therapeutic target across different inflammation-related diseases. Here, we show an acute exercise-induced increase in AHR ligand availability on a systemic level and a kynurenine pathway activation in peripheral blood mononuclear cells (PBMCs). Concurrently, the AHR is activated in PBMCs following acute exercise. Exercise effects on both, kynurenic acid and AHR activation in PBMCs were greater in response to high-intensity interval exercise (50 min., six three-minute intervals á 90% V̇O2peak, and three-minute intervals at 50% V̇O2peak in between) compared to workload-matched moderate intensity continuous exercise (50 min.). In conclusion, these data indicate a novel mechanistic link how exercise modulates the immune system through the kynurenine pathway-AHR axis, potentially underlying exercise-induced benefits in various chronic diseases.

Acute exercise induces changes within the T-cell compartment, especially in cytotoxic CD8(+ )memory subsets, depending on exercise intensity and duration. It is unclear whether exercise-induced changes in major T-cell subsets differ in response to acute high-intensity interval training (HIIT) or moderate-intensity continuous training (MICT) and whether sex-specific effects exist. Twenty-four recreationally active runners (females: n=12, 27.8 +/- 4.1years, 54.4 +/- 4.6 ml*kg(-1)*min(-1); males: n=12, 31.6 +/- 3.8years, 58.9 +/- 7.7 ml*kg(-1)*min(-1)) participated in this randomized controlled crossover study, and conducted an energy- and duration-matched HIIT and MICT session. Blood was sampled before (T-1), immediately (T-2) and 1 h after exercise (T-3). Flow cytometry was used to identify T-cell populations. HIIT decreased the proportion of CD8(+ )T-cells more pronounced at T-3 compared to MICT (p=0.007), induced a significantly stronger increase in the CD8(+ )effector memory (T-EM) cell proportion at T-2 (p=0.032), and decreased CD4(+ )central memory proportion more pronounced at T-2 (p=0.029). A decrease below baseline CD8(+ )T(EM) proportion at T-3 was observed only after HIIT (p<0.001). No interaction effects between sexes were revealed. Taken together, HIIT represents a more potent stimulus to induce shifts mainly within the cytotoxic CD8(+ )T-cell compartment, thereby giving implications to investigate the role of HIIT on the cells effector phenotype and function in more detail.

The kynurenine pathway of tryptophan degradation generates several metabolites such as kynurenine or kynurenic acid that serve as endogenous ligands of the aryl hydrocarbon receptor (AHR). Due to its distinct biological roles particularly modulating the immune system, the AHR is a current therapeutic target across different inflammation-related diseases. Here, we show an exercise-induced increase in AHR ligand availability on a systemic level and a kynurenine pathway activation in peripheral mononuclear blood cells (PBMCs). Concurrently, the AHR is activated in PBMCs following acute exercise, with effects being dependent on exercise intensity. In conclusion, these data indicate a novel mechanistic link how exercise modulates the immune system through the kynurenine pathway-AHR axis, potentially underlying exercise-induced benefits in various chronic diseases.### Competing Interest StatementThe authors have declared no competing interest.

Purpose Acute exercise elicits a transient anti-inflammatory state during the early recovery period. Since recent studies reported on regimen-specific effects on immune-related humoral factors and cellular subsets, this study compared the effects of intensity- and time-matched acute interval and continuous exercise on peripheral anti-inflammatory cellular and humoral immune parameters with a particular focus on the PD-1 expression in CD4 + regulatory T cells (T regs ). Methods Twenty-four recreationally active runners (age: 29.7 ± 4.3 years, BMI: 22.2 ± 2.4, VO 2peak : 56.6 ± 6.4 ml × kg −1 × min −1 ) participated in this crossover RCT. Each subject conducted a moderate continuous (MCE) and a high-intensity interval exercise (HIIE) session in a counterbalanced design. Blood was drawn before, immediately after, and 1 h after exercise. T reg subsets and levels of PD-1 and Foxp3 were assessed by flow cytometry. Serum levels of IL-10 and IL-6 were quantified by ELISA. Results PD-1 levels on T regs increased within the recovery period after HIIE ( p < .001) and MCE ( p < 0.001). Total counts of T regs (HIIE: p = 0.044; MCE: p = .021), naïve T regs (HIIE: p < 0.001; MCE: p < 0.001), and PD-1 + effector T regs (eT regs ) (HIIE: p = .002) decreased 1 h after exercise. IL-10 increased 1 h after HIIE ( p < 0.001) and MCE ( p = 0.018), while IL-6 increased immediately after both HIIE ( p = 0.031) and MCE ( p = 0.021). Correlations between changes in IL-6 and IL-10 ( p = 0.017, r = 0.379) and baseline VO 2peak and T reg frequency ( p = 0.002, r = 0.660) were identified. Conclusion This is the first study that investigates PD-1 expression in circulating T regs after acute exercise, revealing an increase in PD-1 levels on eT regs during the early recovery period after intensity- and time-matched HIIE and MCE. Future studies are needed to investigate the PD-1 signalosome in eT regs , together with the expression of key effector molecules (i.e., IL-10, TGF-β, IL-35, CTLA-4) to elucidate PD-1-dependent changes in cellular function. Based on changes in serum cytokines, this study further reveals a regimen-independent establishment of an anti-inflammatory milieu and underpins the role of the IL-6/IL-10 axis.

BackgroundAge-related accumulation of highly differentiated CD8(+) effector memory re-expressing CD45RA (EMRA) T-cells and disruption of the kynurenine (KYN) pathway are associated with chronic inflammation and the development of insulin resistance.In this study the aim was to investigate the effects of 12-week combined strength and endurance exercise on CD8(+) T-cell differentiation and KYN pathway metabolites. Ninety-six elderly subjects (f/m, aged 50-70) were randomized to a control (CON) or exercise (EX) group. The EX group completed combined strength and endurance training twice weekly for one hour each time at an intensity of 60% of the one-repetition maximum for strength exercises and a perceived exertion of 15/20 for endurance exercises. The EX group was also randomly subdivided into two groups with or without a concomitant balanced diet intervention in order to examine additional effects besides exercise alone. Before and after the intervention phase, the proportions of CD8(+) T-cell subsets and levels of KYN pathway metabolites in peripheral blood were determined.ResultsThe CD8(+) EMRA T-cell subsets increased in the CON group but remained almost unchanged in the EX group (p = .02). Plasma levels of kynurenic acid (KA) increased in the EX group and decreased in the CON group (p = .03). Concomitant nutritional intervention resulted in lower levels of quinolinic acid (QA) compared with exercise alone (p = .03). Overall, there was a slight increase in the QA/KA ratio in the CON group, whereas it decreased in the EX group (p > .05).ConclusionsCombined strength and endurance training seems to be a suitable approach to attenuate CD8(+) T-cell differentiation in the elderly and to redirect the KYN pathway towards KA. The clinical relevance of these effects needs further investigation.

The mobilization and activation of natural killer (NK) cells have been proposed as key mechanisms promoting anti-oncogenic effects of physical exercise. Although mouse models have proven that physical exercise recruits NK cells to tumor tissue and inhibits tumor growth, this preclinical finding has not been transferred to the clinical setting yet. In this first-in-human study, we found that physical exercise mobilizes and redistributes NK cells, especially those with a cytotoxic phenotype, in line with preclinical models. However, physical exercise did not increase NK cell tumor infiltrates. Future studies should carefully distinguish between acute and chronic exercise modalities and should be encouraged to investigate more immune-responsive tumor entities.

The unique contribution of the serotonin transporter-linked polymorphic region (5-HTTLPR), intronic region 2 (STin2), and monoamine oxidase A (MAO-A) genes to individual differences in personality traits has been widely explored, and research has shown that certain forms of these polymorphisms relate to impulsivity and impulsivity-related disorders. Humans showing these traits are also described as having an asymmetrical prefrontal cortical activity when compared to others. In this explorative study, we examine the relationship between serotonergic neurotransmission polymorphisms, cortical activity features (prefrontal alpha asymmetry, individual alpha peak frequency [iAPF]), emotion-related and non-emotion-related impulsivity in humans. 5-HTTLPR, MAO-A, and STin2 polymorphisms were assessed in blood taken from 91 participants with high emotion-related impulsivity levels. Sixty-seven participants completed resting electroencephalography and a more comprehensive impulsivity index. In univariate analyses, iAPF correlated with both forms of emotion-related impulsivity. In multiple linear regression models, 5-HTTLPR polymorphism (model 1, adj. R2 = 15.2%) and iAPF were significant interacting predictors of emotion-related impulsivity, explaining a large share of the results' variance (model 2, adj. R2 = 21.2%). Carriers of the low transcriptional activity 5-HTTPLR and MAO-A phenotypes obtained higher emotion-related impulsivity scores than others did. No significant results were detected for non-emotion-related impulsivity or for a form of emotion-related impulsivity involving cognitive/motivational reactivity to emotion. Our findings support an endophenotypic approach to impulsivity, showing that tri-allelic 5-HTTLPR polymorphism, iAPF, and their interaction are relevant predictors of one form of emotion-related impulsivity.

The kynurenine (KYN) pathway gains growing research interest concerning the genesis, progression and therapy of solid tumors. Previous studies showed exercise-induced effects on metabolite levels along the KYN pathway. Modulations of the KYN pathway might be involved in the positive impact of exercise on prostate cancer progression and mortality. The objective of this trial was to investigate whether a single-physical exercise alters tryptophan (TRP) metabolism and related inflammatory markers in this population. We conducted a randomized controlled trial with 24 patients suffering from prostate cancer. While the control group remained inactive, the intervention group performed a 30-min aerobic exercise on a bicycle ergometer at 75% of individual VO2peak. Before (t0) and directly after the exercise intervention (t1) KYN, TRP, kynurenic acid, quinolinic acid as well as various inflammation markers (IL6, TNF-α, TGF-β) were measured in blood serum. At baseline, the present sample showed robust correlations between TRP, KYN, quinolinic acid and inflammatory markers. Regarding the exercise intervention, interaction effects for TRP, the KYN/TRP ratio and TGF-β were observed. The results show for the first time that acute physical exercise impacts TRP metabolism in prostate cancer patients. Moreover, baseline associations underline the relationship between inflammation and the KYN pathway in prostate cancer.

Background Data on changes in natural killer cell cytolytic activity (NKCA) in response to acute physical exercise are contradictory. Objective The aim of this systematic review, meta-analysis and meta-regression is to (1) examine the effect of acute physical exercise on NKCA, (2) shed more light on the moderating factors, and (3) test the assumption of NKCA suppression subsequent to performing sports. Methods Two comparisons of NKCA were performed: (1) pre- versus post-exercise and (2) pre-exercise versus recovery. Data were acquired through a systematic search of MEDLINE (via PubMed), Scopus, and SportDiscus. Studies were eligible for inclusion if the effect of acute physical exercise was assessed including a passive control group and reporting NKCA prior to and immediately after the trial, and during the first 2 h of recovery. To better explain between-study heterogeneity, a moderator analysis was conducted. Results Pooled estimate from 12 studies reporting 18 effect sizes show that NKCA is largely elevated by acute physical exercise (Hedges’ g = 1.02, 95% CI 0.59–1.46, p < 0.01). Meta-regressions reveal that this effect is larger for endurance versus resistance exercise and increases with the intensity of exercise (both p < 0.01), whereas the blood material used in the assay ( p = 0.71), and the quantitative change in NK-cell count ( R 2 = 0%, p = 0.55) do not play a significant role. Physical exercise does not affect the level of NKCA after the recovery period ( g = 0.06, 95% CI − 0.37 to 0.50, p < 0.76). Conclusions This work provides solid evidence for elevated NKCA through performing sports which returns to baseline during the first 1–2 h of recovery, but not below the pre-exercise values providing counterevidence to the assumption of temporarily reduced NKCA. Remarkably, the functional change in NKCA exists independently from the quantitative change in NK-cell count. PROSPERO registration number: CRD42020134257.

In persons with multiple sclerosis (PwMS), the neutrophil-to-lymphocyte ratio (NLR) is associated with disability status, symptomatology and disease activity. High-intensity interval training (HIIT) improves many symptoms in PwMS and may positively influence disease progression. Here, we present results from a randomized controlled trial during inpatient rehabilitation on immediate (single bout) and training (3-week intervention) effects of HIIT versus moderate continuous training on NLR and related cellular inflammation markers. Only HIIT reduced the NLR over the 3-week intervention period. These training effects might be due to repetitive inflammatory states with compensatory anti-inflammatory counterbalancing after each HIIT session.