Blood-based assessment of oxidative stress, inflammation, endocrine and metabolic adaptations in eventing horses accounting for plasma volume shift after exercise.

BACKGROUND: After submaximal exercise, blood values of eventing horses show physiological reactions. OBJECTIVES: This prospective longitudinal study investigated blood parameters in 20 elite eventing horses before and after two-four-star cross-country rides. METHODS: Using a mixed model adjusting for plasma volume shift, we assessed exercise-dependent parameters and compared blood values with reference ranges for healthy horses at rest. RESULTS: Following exercise, cortisol, triiodothyronine (T3) and thyroxine (T4) showed short-term increases, and superoxide-dismutase showed a small short-term increase. Hepatic values showed short-term (haemoglobin [HGB], globulins) or sustained increases (bilirubin, glutamate dehydrogenase, alanine aminotransferase). Digestion-related parameters showed small short-term increases (α-amylase, triglycerides) or decreases (cholesterol, DGGR-lipase), apparent through plasma shift adjustment. Zinc decreased in the short term, and iron showed a delayed decrease. White blood cell count increased persistently after training, whereas serum amyloid A remained unchanged. CONCLUSIONS: Exercised eventing horses had consistently elevated HGB and cortisol levels 10 and 30 min after submaximal exercise, exceeding the reference ranges for healthy horses at rest. Exercise activates the hypothalamic-pituitary-adrenocortical and hypothalamic-pituitary-thyroid axes. Antioxidant activity was observed. Increased energy requirements led to the mobilization of energy reserves, and a sustained increase in liver enzymes indicated hepatocellular injury. Mild haemolysis suggested increased muscle metabolism, whereas signs of inflammation were subtle. Further research is needed to identify which horses deviate from mean values.

Percutaneous Left Atrial Appendage Occlusion-Current Evidence and Future Directions.

Over the past two decades, percutaneous left atrial appendage occlusion (LAAO) has proven to be a viable alternative to oral anticoagulation (OAC) for stroke prevention in patients with atrial fibrillation (AF), in particular in those patients who are at increased risk for stroke and bleeding complications. This systematic review provides a comprehensive evaluation of anatomical features, patient selection, procedural planning and execution, complications, medical treatment following the procedure, and contemporary outcome data.

A Delphi Study to Determine International and National Equestrian Expert Opinions on Domains and Sub-Domains Essential to Managing Sporthorse Health and Welfare in the Olympic Disciplines.

The public is increasingly questioning equestrianism's social license to operate. While the focus historically centered on horseracing, increased scrutiny is now being placed on how dressage, showjumping, and eventing are addressing equine management and welfare concerns. Nominated equestrian federation and equestrian organization experts (n = 104) directly involved in international and/or national-level horse sports took part in a four-stage, iterative Delphi to obtain consensus on what factors should be considered essential to manage sporthorse health and welfare. Five core domains were agreed as essential: training management, competition management, young horse management, health status and veterinary management, and the horse-human relationship. Two further domains: stable and environmental management, and welfare assessment were rated as important but not essential, as most respondents felt that these areas were already managed well. Participants felt increased education and guidance combined with further policy development and regulation are needed to support stakeholders to optimize sporthorse management. An appetite to engage with research to generate evidence that promotes sporthorse welfare was evident. The development of a sporthorse welfare charter and evidence-based guidelines to inform the management and monitoring of sporthorses' health and welfare are recommended to provide horses with a good life and to safeguard the future of equestrian sports.

Blood-Based Markers for Skeletal and Cardiac Muscle Function in Eventing Horses before and after Cross-Country Rides and How They Are Influenced by Plasma Volume Shift.

Horses competing in cross-country tests are subjected to high physical demands. Within the scope of this prospective longitudinal study, blood values of 20 elite eventing horses were examined before and after two- to four-star cross-country rides. The aim was to find out whether blood-based markers for skeletal muscle and cardiac muscle function change after cross-country exercise. Parameters that provide information about fluid balance, muscle enzymes, metabolites and cardiac muscle-specific markers were investigated. We developed an approach to eliminate the concentration changes caused by reduced plasma volume. Parameters were measured pre, 10 and 30 min post exercise and the next morning and were evaluated using a mixed model. Thirty minutes after exercise, most parameter concentrations changed in an exercise-dependent manner. The next morning, most exercise-related markers recovered rapidly, while creatine kinase (CK) (26% increase; p = 0.008) and lactate dehydrogenase (LDH) (15% increase; p < 0.001) showed a declining but sustained increase. Cardiac troponin I (cTnI) increased above the reference range in 40 of the 55 rides (73%) and in 18 of 20 horses in the morning after exercise.

Multilineage Differentiation Potential of Equine Adipose-Derived Stromal/Stem Cells from Different Sources.

The investigation of multipotent stem/stromal cells (MSCs) in vitro represents an important basis for translational studies in large animal models. The study's aim was to examine and compare clinically relevant in vitro properties of equine MSCs, which were isolated from abdominal (abd), retrobulbar (rb) and subcutaneous (sc) adipose tissue by collagenase digestion (ASCs-SVF) and an explant technique (ASCs-EXP). Firstly, we examined proliferation and trilineage differentiation and, secondly, the cardiomyogenic differentiation potential using activin A, bone morphogenetic protein-4 and Dickkopf-1. Fibroblast-like, plastic-adherent ASCs-SVF and ASCs-EXP were obtained from all sources. The proliferation and chondrogenic differentiation potential did not differ significantly between the isolation methods and localizations. However, abd-ASCs-EXP showed the highest adipogenic differentiation potential compared to rb- and sc-ASCs-EXP on day 7 and abd-ASCs-SVF a higher adipogenic potential compared to abd-ASCs-EXP on day 14. Osteogenic differentiation potential was comparable at day 14, but by day 21, abd-ASCs-EXP demonstrated a higher osteogenic potential compared to abd-ASCs-SVF and rb-ASCs-EXP. Cardiomyogenic differentiation could not be achieved. This study provides insight into the proliferation and multilineage differentiation potential of equine ASCs and is expected to provide a basis for future preclinical and clinical studies in horses.

Analytical Performance Evaluation of the New GEM® Premier™ 5000 in Comparison to the Epoc® Blood Gas Analyzer in Horses.

Different blood gas analyzers are used in equine practice. Every machine needs to be validated, as they have not been designed for use in horses. The aim of this study was to compare the newly marketed GEM5000 machine to the formerly validated epoc machine for blood gas analysis in horses. In this prospective, non-blinded, comparative laboratory analyzer study, 43 equine blood samples were analyzed on both analyzers and values were compared between the two machines via Lin's concordance analysis, Passing-Bablok regression analysis and Bland-Altman plots. Duplicate measurements were conducted on the GEM5000 machine to evaluate precision. The GEM5000 failed to achieve the required precision for tHb, Hct and iCa2+, but achieved acceptable precision for all other parameters. Concordance correlation analysis revealed poor correlation for Na+, Cl-, iCa2+, K+, Hct and tHb, while there was an at least moderate agreement for all other parameters. Passing-Bablok regression revealed significant constant bias for pCO2, pO2, Cl-, and iCa2+ and significant proportional bias for pCO2, iCa2+ and SO2. Bland-Altman analysis revealed significant systematic bias for Na+, Cl-, iCa2+, K+, Hct, tHb and SO2. This study shows that while precision of the GEM5000 is good, values should not be used interchangeably with data obtained from other blood gas analyzers.

Predictors of Clinical Outcome After Early Veno-Arterial Extracorporeal Membrane Oxygenation in Cardiogenic Shock Complicating ST-Elevation Myocardial Infarction.

OBJECTIVES: Despite increasing use of veno-arterial extracorporeal membrane oxygenation (VA-ECMO) in patients with cardiogenic shock (CS) secondary to ST-segment elevation myocardial infarction (STEMI), a paucity of adequate evidence for this therapy remains. The aim of this single-center clinical registry study was to identify predictors of survival and discern the possible optimal time to initiate VA-ECMO in this cohort. METHODS AND RESULTS: Seventy-nine consecutive patients with CS complicating STEMI who received VA-ECMO support were included in this analysis. The primary endpoint was survival at 6 months after initiation of VA-ECMO. Mean age was 60 ± 11 years. Forty-six patients (58%) were successfully weaned from VA-ECMO and 30 patients (38%) could be discharged. Of these, 23 patients (29% of the overall population) survived up to 6-month follow-up. Multivariate analysis to identify determinants of survival showed no association between the time of CS onset to VA-ECMO start time and 6-month survival (P=.75). Glomerular filtration rate on admission (P<.001), white blood cell count on admission (P≤.01), age (P≤.01), and arterial lactate level 1 and 24 hours after VA-ECMO initiation (P=.01) were the strongest predictors of survival. CONCLUSIONS: The timing of VA-ECMO initiation in patients with CS complicating STEMI was not a prognostic factor of survival. Renal function, white blood cell count, age, and lactate level were the strongest predictors of death during 6-month follow-up.

Monitoring Performance in Show Jumping Horses: Validity of Non-specific and Discipline-specific Field Exercise Tests for a Practicable Assessment of Aerobic Performance.

Show jumping is a highly specialized equestrian discipline that requires technical skill but also power and fitness. Monitoring the horses' aerobic performance is therefore essential in order to verify whether the training has induced the desired cardiovascular and muscular adaptations. This study therefore aimed at evaluating the validity of non-specific and discipline-specific field exercise tests for objective evaluation of aerobic performance in show jumpers. For this purpose, data obtained from horses competing at Junior and Young Rider level during show jumping competitions as well as field exercise tests were retrospectively analyzed. The effect of the level of difficulty, the horses' age, the penalty score and the horses' previous level of performance on blood lactate concentrations after show jumping competitions (100 observations in 49 horses) was evaluated by linear mixed effects models (horse as random effect). Estimated marginal means significantly increased from 140 (4.1 mmol/L) to 150 cm (5.2 mmol/L) classes (P = 0.02). Furthermore, post-exercise lactate values significantly increased with the horses' age (P = 0.001). Another group of 12 horses performed a standardized incremental field exercise test on a track (SETtrack), a standardized show jumping course (SETcourse) and a standardized grid exercise (SETgrid) each on three consecutive days. Indices of aerobic performance, derived from the SETtrack [velocity at a heart rate of 140 bpm (V140) and at a lactate concentration of 2 mmol/L (V La2 )] were highly correlated with heart rate (V140: r = -0.75, P = 0.005; V La2 : r =-0.66, P = 0.02) and lactate (V140: r = -0.73, P = 0.02; V La2 : r = -0.72, P = 0.02) in response to SETcourse as well as heart rate during SETgrid (V140: r = -0.73, P = 0.02; V La2 : r = -0.76, P = 0.01). Subjective rating of muscular fatigue was significantly correlated to the mean heart rate during SETcourse (r = -0.64, P = 0.05) and SETgrid (r = -0.74, P = 0.02) but not to the aerobic indices calculated from SETtrack. Besides non-specific incremental field tests, performance monitoring in show jumpers should therefore also include discipline-specific tests that more closely reflect the internal load induced by show jumping competitions.

Structured telephone support programs in chronic heart failure may be affected by a learning curve.

AIMS: The efficacy of a telephone support program in chronic heart failure has been questioned particularly when considering short-term follow-up. This study is aimed to assess the impact of the HeartNetCare telephone support program in chronic heart failure within 18 months of observation and to verify a possible effect of a learning-to-care curve on outcome. METHODS: We retrospectively compared a cohort of 269 chronic heart failure patients included in HeartNetCare program with 200 patients receiving usual care as a control group. All-cause death and hospitalization for heart failure or implantation of left ventricular assist device were the primary composite outcome. Secondary endpoints were the changes in left ventricular ejection fraction and in New York Heart Association (NYHA) functional class. Outcome data were also analyzed in relation to the time of enrollment from program initiation. RESULTS: At baseline, HeartNetCare group showed lower ejection fraction and higher NYHA class. At the follow-up, 59 HeartNetCare patients (21.9%) and 49 usual care patients (24.5%) reached the primary endpoint (P = 0.51). After 18 months of follow-up, HeartNetCare patients improved ejection fraction and NYHA class compared with the usual care patients (P < 0.001). We also observed that the HeartNetCare patients enrolled after 12 months from the initiation of the program had a more favorable outcome in primary endpoint compared with controls. CONCLUSION: These results indicate that the long-term impact of a structured telephone support program might be able to positively influence symptoms and reduce events in chronic heart failure. These appreciable effects where more evident after an initial period essential for completing the learning-to-care curve.

Traditional and quantitative analysis of acid-base and electrolyte imbalances in horses competing in cross-country competitions at 2-star to 5-star level.

BACKGROUND: Early recognition and management of acid-base, fluid, and electrolyte disorders are crucial for the maintenance of health and performance in equine athletes. OBJECTIVES: To analyze changes in acid-base and electrolyte status associated with exercise during cross-country competitions at different levels using traditional and quantitative approaches. ANIMALS: Thirty-eight eventing horses. METHODS: Prospective observational study. Jugular venous blood samples were collected before and after the cross-country test of 25 international eventing competitions ranging from 2-star (formerly 1-star) to 5-star (formerly 4-star) level. Blood gas analysis was performed to determine pH, pCO2 , Na+ , Cl- , and K+ and calculate HCO3 - , tCO2 base excess (BEECF ), anion gap (AG), strong ion difference calculated from Na+ , K+ , Cl- , and lactate- (SID4 ), strong ion difference calculated from Na+ , K+ , and Cl- (SID3 ), strong ion gap (SIG), and total nonvolatile weak buffer concentration (Atot ). Postexercise acid-base imbalances, diagnosed on the basis of the traditional approach, and the simplified strong ion model were compared. RESULTS: Significant decreases in pH, Cl- , SID4 , pCO2 , HCO3 - , tCO2 , and BEECF as well as increases in K+ , SID3 , AG, TP, and Atot were observed between pre- and postexercise samples. The changes in acid-base parameters were significantly affected by the competition level. Using the strong ion approach, a higher proportion of horses was diagnosed with postexercise metabolic acidosis. CONCLUSIONS AND CLINICAL IMPORTANCE: Regarding the complex acid-base changes in horses competing at cross-country competitions, the quantitative approach provided a more detailed analysis of the different factors contributing to acid-base balance than did the traditional approach.

Comparison of two portable clinical analyzers to one stationary analyzer for the determination of blood gas partial pressures and blood electrolyte concentrations in horses.

Portable blood gas analyzers are used to facilitate diagnosis and treatment of disorders related to disturbances of acid-base and electrolyte balance in the ambulatory care of equine patients. The aim of this study was to determine whether 2 portable analyzers produce results in agreement with a stationary analyzer. Blood samples from 23 horses hospitalized for various medical reasons were included in this prospective study. Blood gas analysis and electrolyte concentrations measured by the portable analyzers VetStat and epoc were compared to those produced by the cobas b 123 analyzer via concordance analysis, Passing-Bablok regression and Bland-Altman analysis. Limits of agreement indicated relevant bias between the VetStat and cobas b 123 for partial pressure of oxygen (pO2; 27.5-33.8 mmHg), sodium ([Na+]; 4.3-21.6 mmol/L) and chloride concentration ([Cl-]; 0.3-7.9 mmol/L) and between the epoc and cobas b 123 for pH (0.070-0.022), partial pressure of carbon dioxide (pCO2; 3.6-7.3 mmHg), pO2 (36.2-32.7 mmHg) and [Na+] (0.38.1 mmol/L). The VetStat analyzer yielded results that were in agreement with the cobas b 123 analyzer for determination of pH, pCO2, bicarbonate ([HCO3-]) and potassium concentration [K+], while the epoc analyzer achieved acceptable agreement for [HCO3-] and [K+]. The VetStat analyzer may be useful in performing blood gas analysis in equine samples but analysis of [Na+], [Cl-] and pO2 should be interpreted with caution. The epoc delivered reliable results for [HCO3-] and [K+], while results for pH, pCO2, pO2 and [Na+] should be interpreted with caution.

New insights into valve-related intramural and intracellular bacterial diversity in infective endocarditis.

AIMS: In infective endocarditis (IE), a severe inflammatory disease of the endocardium with an unchanged incidence and mortality rate over the past decades, only 1% of the cases have been described as polymicrobial infections based on microbiological approaches. The aim of this study was to identify potential biodiversity of bacterial species from infected native and prosthetic valves. Furthermore, we compared the ultrastructural micro-environments to detect the localization and distribution patterns of pathogens in IE. MATERIAL AND METHODS: Using next-generation sequencing (NGS) of 16S rDNA, which allows analysis of the entire bacterial community within a single sample, we investigated the biodiversity of infectious bacterial species from resected native and prosthetic valves in a clinical cohort of 8 IE patients. Furthermore, we investigated the ultrastructural infected valve micro-environment by focused ion beam scanning electron microscopy (FIB-SEM). RESULTS: Biodiversity was detected in 7 of 8 resected heart valves. This comprised 13 bacterial genera and 16 species. In addition to 11 pathogens already described as being IE related, 5 bacterial species were identified as having a novel association. In contrast, valve and blood culture-based diagnosis revealed only 4 species from 3 bacterial genera and did not show any relevant antibiotic resistance. The antibiotics chosen on this basis for treatment, however, did not cover the bacterial spectra identified by our amplicon sequencing analysis in 4 of 8 cases. In addition to intramural distribution patterns of infective bacteria, intracellular localization with evidence of bacterial immune escape mechanisms was identified. CONCLUSION: The high frequency of polymicrobial infections, pathogen diversity, and intracellular persistence of common IE-causing bacteria may provide clues to help explain the persistent and devastating mortality rate observed for IE. Improved bacterial diagnosis by 16S rDNA NGS that increases the ability to tailor antibiotic therapy may result in improved outcomes.

Frequency and clinical course of cerebral embolism in patients undergoing transcatheter left atrial appendage closure.

AIMS: The aim of this study was to assess silent and clinically apparent cerebral embolic events in patients undergoing transcatheter left atrial appendage closure. METHODS AND RESULTS: In this prospective single-centre study, 28 patients underwent percutaneous closure of the left atrial appendage. In all patients, a diffusion-weighted magnetic resonance imaging (DW-MRI) study was performed before, the day after the procedure, and during routine follow-up after 45 days. All patients underwent neurological assessment at the time of DW-MRI. Additionally, transcranial Doppler ultrasound monitoring (TCD) for the detection of microembolic material during the procedure was performed. The procedure was successfully completed in all patients. New embolic lesions were detected in nine patients (32%) after the procedure, of which three (33%) were detectable as gliotic lesions at follow-up. One (3.6%) new lesion was observed at 45-day follow-up. Neurological assessment showed no neurological deficits. We observed no relationship between the numbers of microembolic signals on TCD monitoring and the occurrence of cerebral infarctions on DW-MRI. CONCLUSIONS: New cerebral embolic events occur after transcatheter closure of the left atrial appendage. However, most of the lesions demonstrate no gliotic transformation at follow-up. In all patients, the cerebral lesions were clinically unapparent.

Chronic heart failure and aging - effects of exercise training on endothelial function and mechanisms of endothelial regeneration: Results from the Leipzig Exercise Intervention in Chronic heart failure and Aging (LEICA) study.

BACKGROUND: A reduction in number and function of endothelial progenitor cells (EPCs) occurs in both physiologic aging and chronic heart failure (CHF). We assessed whether disease and aging have additive effects on EPCs or whether beneficial effects of exercise training are diminished in old age. METHODS: We randomized 60 patients with stable CHF and 60 referent controls to a training or a control group. To detect possible aging effects we included subjects below 55 (young) and above 65 years (older). Subjects in the training group exercised four times daily at 60% to 70% of VO2max for four weeks under supervision. At baseline and after the intervention the number and function of EPCs were assessed. RESULTS: As compared with young referent controls, older referent controls showed at baseline a reduced EPC number (young: 190 ± 37 CD34/KDR positive cells/ml blood; older: 131 ± 26 CD34/KDR positive cells/ml blood; p < 0.05) and function (young: 230 ± 41 migrated cells/1000 plated cells; older: 185 ± 28 cells/1000 plated cells; p < 0.05). In young and older CHF patients EPC-number (young: 85 ± 21 CD34/KDR positive cells/ml blood; older: 78 ± 20 CD34/KDR positive cells/ml blood) and EPC-function (young: 113 ± 26 cells/1000 plated cells; older: 120 ± 27 cells/1000 plated cells) were impaired. As a result of exercise training, EPC function improved by 24% in older referent controls (p < 0.05), while it remained unchanged in young training referent controls and controls respectively. In young and older patients with CHF four weeks of exercise training resulted in a significant improvement in EPC numbers and EPC function (young: number +66% function +43%; p < 0.05; older: number +69% function +36%; p < 0.05). These results were accompanied by a significant increase in flow mediated dilatation in the training groups of young/older CHF patients and in older referent controls. CONCLUSIONS: Four weeks of exercise training are effective in improving EPC number and EPC function in CHF patients. These training effects were not impaired among older patients, emphasizing the potentials of rehabilitation interventions in a patient group where CHF has a high prevalence.

Bariatric surgery in severely obese adolescents improves major comorbidities including hyperuricemia.

OBJECTIVE: Serum uric acid (sUA) is believed to contribute to the pathogenesis of metabolic comorbidities like hypertension, insulin-resistance (IR) and endothelial dysfunction (EDF) in obese children. The present pilot study investigated the association between sUA concentrations and loss of body weight following laparoscopic sleeve gastrectomy (LSG) or laparoscopic Roux-en-Y-gastric bypass (RYGB) in severely obese adolescents. MATERIALS/METHODS: 10 severely obese adolescents underwent either LSG (n=5) or RYGB (n=5). 17 normal weight, healthy, age- and gender-matched adolescents served as a normal weight peer group (NWPG). Pre- and 12 months postoperatively, sUA and relevant metabolic parameters (glucose homeostasis, transaminases, lipids) were compared. RESULTS: Preoperatively, sUA was significantly elevated in patients with severe obesity compared to NWPG. Twelve months after LSG and RYGB, a significant decrease in sUA, BMI, CVD risk factors, hepatic transaminases, and HOMA-IR was observed. Reduction in SDS-BMI significantly correlated with changes in sUA. CONCLUSIONS: sUA levels and metabolic comorbidities improved following bariatric surgery in severely obese adolescents. The impact of changes in sUA on long-term clinical complications of childhood obesity deserves further study.

Serum vaspin concentrations are decreased after exercise-induced oxidative stress.

Elevated visceral adipose tissue-derived serpin (vaspin) serum concentrations are associated with impaired insulin sensitivity, but increase unexpectedly after long-term physical training. We therefore investigated the effect of an acute exercise bout and the effects of vitamin supplementation on chronic exercise effect and on serum vaspin concentrations. We measured serum vaspin and thiobarbituric acid-reactive substances (TBARS) concentrations in 80 individuals before and after a 1-hour acute exercise bout and independently in 40 healthy young men who were randomly assigned to either antioxidant (vitamin C (1,000 mg/day) and vitamin E (400 IU/day)) or to no supplementation after a standardized 4-week physical training program as a post hoc analysis. Serum vaspin concentrations significantly decreased after acute physical exercise as well as after 4 weeks of training in individuals without antioxidants. Changes in vaspin serum concentration correlate with increased TBARS serum concentrations both in response to a 1-hour exercise bout (r = -0.42, p < 0.01) and to the 4-week training (r = -0.31, p < 0.05). Interestingly, supplementation with antioxidants rather increased circulating vaspin levels in response to 4 weeks of exercise. In conclusion, vaspin serum concentrations are decreased by exercise-induced oxidative stress, but not by exercise-associated improvement in insulin sensitivity.

Long-term exercise training decreases interleukin-6 (IL-6) serum levels in subjects with impaired glucose tolerance: effect of the -174G/C variant in IL-6 gene.

OBJECTIVE: Exercise training has been shown to have anti-inflammatory effects in patients with type 2 diabetes. Changes in interleukin-6 (IL-6) serum concentrations in response to training could contribute to these beneficial effects. However, there are heterogeneous data on whether circulating IL-6 is altered by exercise training. We therefore hypothesize that genetic factors modify the individual changes in IL-6 levels after long-term training. RESEARCH DESIGN AND METHODS: The -174G/C variant in the IL-6 gene was genotyped in 60 subjects with impaired glucose tolerance. For a 12-month interventional study, patients were randomized into three groups: a control group (n=16) was compared with one group, which underwent a standardized training program (n=24) and another group, which was treated with 4 mg rosiglitazone once daily (n=20). At baseline, after 1, 6, and 12 months, we measured anthropometric parameters and serum concentration of IL-6 and, at baseline and after 12 months, we determined glucose tolerance and fitness level. RESULTS: Only in subjects carrying the SNP -174C allele did long-term exercise training result in significantly reduced IL-6 serum concentrations. Multivariate linear regression analysis identified the IL-6 genotype as a significant predictor of changes in IL-6 serum concentrations independent of age, gender and improvement in body mass index, hemoglobin (Hb)A(1c), and fitness level in response to training. CONCLUSIONS: Genetic variants in the IL-6 gene significantly modify changes in IL-6 serum concentrations in response to long-term exercise training programs. Our data suggest that genetic factors are important determinants for the individual response to anti-inflammatory effects of exercise training.