Level of IL-6, TNF, and IL-1ß and age-related diseases: a systematic review and meta-analysis.

Introduction: Chronic low-grade inflammation is an important aspect of morbidity and mortality in older adults. The level of circulating pro-inflammatory cytokines (interleukin (IL)-6, tumor necrosis factor (TNF) or IL-1ß) is a risk factor in cardiovascular and neurodegenerative diseases and is also associated with sarcopenia and frailties. The objective of this study was to assess each cytokine: IL-6, TNF, and IL-1ß separately in the elderly with comorbidities against controls without diseases according to the data published in the available literature. Methods: The electronic bibliographic PubMed database was systematically searched to select all the relevant studies published up to July 2023. The total number of the subjects involved in the meta-analysis included patients with diseases (n=8154) and controls (n=33967). Results: The overall concentration of IL-6 was found to be higher in patients with diseases compared to controls and the difference was statistically significant, with a p-value of <0.001 (SMD, 0.16; 95% CI, 0.12-0.19). The heterogeneity was considerable with Q = 109.97 (P <0.0001) and I2 = 79.2%. The potential diagnostic usefulness of IL-6 was confirmed by odds ratio (OR) analysis (OR: 1.03, 95% CI (1.01; 1.05), p=0.0029). The concentration of both TNF and IL-1ß was elevated in the control group compared to patients and amounted to SMD -0.03; 95% CI, -0.09-0.02, p-value 0.533 and SMD-0.29; 95% CI, -0.47- -0.12; p = 0.001, respectively. For TNF, however, the difference was statistically insignificant. Discussion: IL-6, unlike TNF and IL-1ß, could be a useful and convenient marker of peripheral inflammation in older adults with various comorbidities.

Does excess body weight accelerate immune aging?

BACKGROUND: Overweight and obesity in older adults increase the risk of a range of comorbidities by sustaining chronic inflammation and thus enhancing immunosenescence. This study aimed to assess whether excess body mass affected disproportion in T lymphocytes. Therefore, the study was designed to explain whether excess body mass in older individuals affected the disproportion in numbers of T lymphocytes and whether anthropometric indices and immune risk profile expressed as CD4/CD8 ratio are diagnostically useful in the analysis of immunosenescence. MATERIALS & METHODS: One hundred three individuals aged 73.6 ± 3.1 years were allocated to the normal body mass (body mass index (BMI) 18.5-24.9 kg/m2,n = 39), the pre-obesity (BMI 25.0-29.9 kg/m2, n = 44) or the obesity (BMI ≥30.0 kg/m2, n = 20) group, based on WHO recommendations. Details on the subjects' medical history and lifestyle were obtained by health questionnaire. Anthropometric analysis was performed by bioelectrical impedance method, biochemical analysis was made by the automatic analyzer and ELISA immunoassays, and T and B lymphocyte counts were determined by eight-parameter flow cytometry. Additionally, visceral adiposity index, body adiposity index (BAI), and body shape index (ABSI) were evaluated based on body circumference, BMI and lipid-lipoprotein profile measurements. RESULTS: The highest percentage of CD3+CD4+ T lymphocytes (59.4 ± 12.6 %) and the lowest CD3+CD8+ T lymphocytes (31.6 ± 10.0 %) were noted in patients the obesity group. The highest cut-off value of 1.9 for CD4/CD8 ratio was recorded in the normal body mass vs pre-obesity model. CD4/CD8 ratio > 2.5 was recorded in >20 % of our pre-obesity and obesity groups while 64.5 % of the normal body mass group had CD4/CD8 ratio < 1. High diagnostic usefulness was demonstrated for both BAI and lipid accumulation product (LAP) (AUC values of ~0.800 and ~ 0.900 respectively) in three models: normal body mass vs pre-obesity, normal body mass vs obesity, and pre-obesity vs obesity. CONCLUSION: The odds ratios (OR) for CD4/CD8 ratio in the normal body mass vs obesity model (OR = 16.1, 95%CI 3.8-93.6) indicated a potential diagnostic value of T lymphocytes for clinical prognosis of immune aging in relation to excess body weight in older adults. High values of AUC obtained for the following models: CD4/CD8 + BAI (AUC = 0.927), CD4/CD8 + LAP (AUC = 1.00), CD4/CD8 + ABSI (AUC = 0.865) proved to provide excellent discrimination between older adults with obesity and with normal body mass.

Diagnostics of inflammaging in relation to sarcopenia.

One of the theories about aging focuses on the immune response and relates to the activation of subclinical and chronic inflammation. This study was designed to investigate the relationship between inflammation and sarcopenia and to evaluate the influence of lifestyle on the inflammatory profile. Finally, therapeutic strategies to counteract the pathophysiological effect of skeletal muscle aging were also indicated. One hundred seventy-three individuals aged 71.5 ± 6.8 years were divided into two groups: sarcopenia and probable sarcopenia (n = 39) and no sarcopenia (n = 134). Sarcopenia was assessed according to the algorithm of the European Working Group on Sarcopenia in the older adults 2. C-reactive protein (CRP) (p = 0.011) and CRP/albumin ratio (p = 0.030) as well as IL-1ß (p = 0.002), cfDNA (p < 0.001) and bilirubin levels (p = 0.002) were significantly higher in the sarcopenia group as opposed to the no sarcopenia group. No significant differences were observed between groups in the concentration of TNFα (p = 0.429) and IL-6 (p = 0.300). An inverse correlation was found between gait speed and cfDNA (rs = -0.234, p < 0.01) and IL-1ß (rs = -0.263, p < 0.01). The ROC analysis of cfDNA, CRP, IL-1ß and bilirubin ranged from 0.6 to 0.7, which confirms the association between sarcopenia and inflammatory mediators and indicates high clinical usefulness of cfDNA and bilirubin in sarcopenia prediction. We also indicated a link between inflammation and fitness level in the older adult thereby providing evidence that lifestyle exercise should be a key therapeutic strategy in sarcopenia prevention.

The Role of Inflammation in Age-Associated Changes in Red Blood System.

Aging-related anemia contributes to frailty syndrome, cognitive decline and early mortality. The study aim was to evaluate inflammaging in relation to anemia as a prognostic indicator in affected older patients. The participants (73.0 ± 7.2 years) were allocated into anemic (n = 47) and non-anemic (n = 66) groups. The hematological variables RBC, MCV, MCH, RDW, iron and ferritin were significantly lower, whereas erythropoietin EPO and transferrin Tf tended toward higher values in the anemic group. Approx. 26% of individuals demonstrated transferrin saturation TfS < 20%, which clearly indicates age-related iron deficiency. The cut-off values for pro-inflammatory cytokine IL-1ß, TNFα and hepcidin were 5.3 ng/mL, 97.7 ng/mL and 9.4 ng/mL, respectively. High IL-1ß negatively affected Hb concentration (rs = -0.581, p < 0.0001). Relatively high odds ratios were observed for IL-1ß (OR = 72.374, 95%Cl 19.688-354.366) and peripheral blood mononuclear cells CD34 (OR = 3.264, 95%Cl 1.263-8.747) and CD38 (OR = 4.398, 95%Cl 1.701-11.906), which together indicates a higher probability of developing anemia. The results endorse the interplay between inflammatory status and iron metabolism and demonstrated a high usefulness of IL-1ß in identification of the underlying causes of anemia, while CD34 and CD38 appeared useful in compensatory response assessment and, in the longer term, as part of a comprehensive approach to anemia monitoring in older adults.

Assessment of metabolic syndrome predictors in relation to inflammation and visceral fat tissue in older adults.

The diagnosis of metabolic syndrome (MetS) focuses on the assessment of risk factors such as insulin resistance, dyslipidemia, central adiposity and elevated blood pressure. Evidence suggests that markers of systemic inflammation may also be included in the definition of MetS and play some role in its pathogenesis. The study was designed to evaluate low-grade inflammation status in older adults with MetS in relation to increased body fat tissue and an attempt was made to evaluate new predictors for MetS through the analysis of the ROC Curve. Ninety-six middle-aged (69.2 ± 4.9) individuals from University of Third Age (women n = 75 and men n = 21) were allocated to two groups: without metabolic syndrome (n = 37) and with metabolic syndrome (n = 59) according to International Diabetes Federation criteria in agreement with American Heart Association/National Heart, Lung and Blood Institute 2009. Participants' current health status was assessed using medical records from a routine follow-up visit to a primary care physician. Statistical analysis was performed using R studio software. Depending on the normal distribution, ANOVA or the Kruskal-Wallis test was used. The optimal threshold value for clinical stratification (cut-off value) was obtained by calculating the Youden index. The AUC was observed to be the highest for a new anthropometric index i.e. lipid accumulation product (0.820). Low-grade inflammation dominated in MetS group (BMI 28.0 ± 4.4 kg/m2, WHR 0.9 ± 0.1, FM 24.7 ± 7.9 kg) where significantly higher values of TNF-α (p = 0.027) and HGMB-1 protein (p = 0.011) were recorded.The optimal threshold values for immunological indices assessed as new predictors of the metabolic syndrome were: 93.4 for TNF-α, 88.2 for HGMB-1 protein and 1992.75 for ghrelin. High AUC values for these indices additionally confirmed their high diagnostic usefulness in MetS.

Immunosenescence in Aging-Related Vascular Dysfunction.

The immunosenescence-related disproportion in T lymphocytes may have important consequences for endothelial dysfunction, which is a key event in vascular aging. The study was designed to assess the prognostic values of the inflammatory-immune profile to better predict and prevent vascular diseases associated with old age. Eighty individuals aged 70.9 ± 5.3 years were allocated to a low- (LGI) or high-grade inflammation (HGI) group based on CRP (<3 or ≥3 mg/L) as a conventional risk marker of cardiovascular diseases. Significant changes in inflammatory and endothelium-specific variables IL-1ß, IL-6, TNFα, oxLDL, H2O2, NO, 3-nitrotyrosine, and endothelial progenitor cells (OR 7.61, 95% CI 2.56−29.05, p < 0.0001), confirmed their interplay in vascular inflammation. The flow-cytometry analysis demonstrated a high disproportion in T lymphocytes CD4+ and CD8+ between LGI and HGI groups. CRP was <3 mg/mL for the CD4/CD8 ratio within the reference values ≥ 1 or ≤2.5, unlike for the CD4/CD8 ratio < 1 and >2.5. The odds ratios for the distribution of CD4+ (OR 5.98, 95% CI 0.001−0.008, p < 0.001), CD8+ (OR 0.23, 95% CI 0.08−0.59, p < 0.01), and CD8CD45RO+ T naïve cells (OR 0.27, 95% CI 0.097−0.695, p < 0.01) and CD4/CD8 (OR 5.69, 95% CI 2.07−17.32, p < 0.001) indicated a potential diagnostic value of T lymphocytes for clinical prognosis in aging-related vascular dysfunction.

Prognostic Values of Combined Ratios of White Blood Cells in Glioblastoma: A Retrospective Study.

In some malignant tumours, the changes in neutrophil counts in relation to other blood cells are connected with unfavourable prognosis. Nevertheless, the prognostic value of the combinations of the haematological components in glioblastoma (GBM) remains under dispute. The clinical significance of the neutrophil-to-lymphocyte ratio (NLR), systemic immune inflammation index (SII), and systemic inflammation response index (SIRI) was investigated in our study. We retrospectively studied 358 patients (males n = 195; females n = 163) aged 59.9 ± 13.5 yrs with newly diagnosed glioma and admitted to the Neurosurgery Centre. Routine blood tests and clinical characteristics were recorded within the first hour of hospital admission. The inflammatory variables: NLR, SII and SIRI exceeded the reference values and were significantly elevated in Grade 3 and Grade 4 tumour. The Cox model analysis showed that the age ≥ 63 years, NLR ≥ 4.56 × 103/µL, SII ≥ 2003 × 103/µL and SIRI ≥ 3.03 × 103/µL significantly increased the risk of death in Grade 4 tumour patients. In the inflammatory variables, NLR demonstrated the highest impact on the survival time (HR 1.56; 95% CI 1.145-2.127; p = 0.005). In the first Polish study including GBM patients, the age in relation to simple parameters derived from complete blood cell count were found to have prognostic implications in the survival rate.

Inflammatory Predictors of Prognosis in Patients with Traumatic Cerebral Haemorrhage: Retrospective Study.

We aimed to evaluate the relationship between neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), lymphocyte to monocyte ratio (LMR), systemic inflammation index (SII), and Glasgow Coma Scale (GCS) score in patients with traumatic intracerebral haemorrhage (TICH). We retrospectively investigated 95 patients with TICH hospitalised at the Neurosurgery Department in Zielona Gora from January 2017 to March 2021. Routine blood tests were performed 5 h after injury. NRL and SII were significantly higher in patients with GCS ≤ 8 than patients with GCS > 8 and exceeded reference values in 95% of patients. GCS was inversely correlated with NLR and SII. Receiver operating characteristic (ROC) analysis confirmed the value of NLR and SII regarding GCS score; Area Under the Curve (AUC) 0.748, 95% Confidence Interval (CI) 0.615-0.880. An optimised NLR cut-off value of 0.154 was identified with a sensitivity of 0.90 and specificity of 0.56. The value of SII regarding GCS was confirmed with ROC curves; AUC 0.816, 95% CI 0.696-0.935. An optimised NLR cut-off value of 0.118 was identified with a sensitivity of 0.95 and specificity of 0.57. NLR and SII are significantly related to GCS scores and are promising predictors of clinical prognosis in TICH patients.

Pre-Existing Hypertension Is Related with Disproportions in T-Lymphocytes in Older Age.

Age-related immune deficiencies increase the risk of comorbidities and mortality. This study evaluated immunosenescence patterns by flow cytometry of naïve and memory T cell subpopulations and the immune risk profile (IRP), expressed as the CD4/CD8 ratio and IgG CMV related to comorbidities. The disproportions in naïve and memory T cells, as well as in the CD4/CD8 ratio, were analysed in 99 elderly individuals (71.9 ± 5.8 years) diagnosed with hypertension (n = 51) or without hypertension (n = 48), using an eight-parameter flow cytometer. The percentage of CD4+ T lymphocytes was significantly higher in hypertensive than other individuals independently from CMV infections, with approximately 34% having CD4/CD8 > 2.5, and only 4% of the elderly with hypertension having CD4/CD8 < 1. The elderly with a normal BMI demonstrated the CD4/CD8 ratio ≥ 1 or ≤ 2.5, while overweight and obese participants showed a tendency to an inverted CD4/CD8 ratio. CD4/CD8 ratio increased gradually with age and reached the highest values in participants aged >75 years. The decline in CD4+ naïve T lymphocytes was more prominent in IgG CMV+ men when compared to IgG CMV+ women. The changes in naïve and memory T lymphocyte population, CD4/CD8, and CMV seropositivity included in IRP are important markers of health status in the elderly that are dependent on hypertension.

The Association of Anti-Inflammatory Diet Ingredients and Lifestyle Exercise with Inflammaging.

One of the latest theories on ageing focuses on immune response, and considers the activation of subclinical and chronic inflammation. The study was designed to explain whether anti-inflammatory diet and lifestyle exercise affect an inflammatory profile in the Polish elderly population. Sixty individuals (80.2 ± 7.9 years) were allocated to a low-grade inflammation (LGI n = 33) or high-grade inflammation (HGI n = 27) group, based on C-reactive protein concentration (<3 or ≥3 mg/L) as a conventional marker of systemic inflammation. Diet analysis focused on vitamins D, C, E, A, ß-carotene, n-3 and n-6 PUFA using single 24-h dietary recall. LGI demonstrated a lower n-6/n-3 PUFA but higher vitamin D intake than HGI. Physical performance based on 6-min walk test (6MWT) classified the elderly as physically inactive, whereby LGI demonstrated a significantly higher gait speed (1.09 ± 0.26 m/s) than HGI (0.72 ± 0.28 m/s). Circulating interleukins IL-1ß, IL-6, IL-13, TNFα and cfDNA demonstrated high concentrations in the elderly with low 6MWT, confirming an impairment of physical performance by persistent systemic inflammation. These findings reveal that increased intake of anti-inflammatory diet ingredients and physical activity sustained throughout life attenuate progression of inflammaging in the elderly and indicate potential therapeutic strategies to counteract pathophysiological effects of ageing.

Assessment of Serum Neopterin as a Biomarker in Peripheral Artery Disease.

Neopterin (NPT), a pyrazino-pyrimidine compound mainly produced by activated macrophages, has been regarded as a proinflammatory and proatherosclerotic agent. The study was designed to evaluate NPT level and its interaction with conventional peripheral artery disease (PAD) biomarkers and vascular regenerative potential in severe PAD. The study included 59 patients (females n = 17, males n = 42) aged 67.0 ± 8.2 years classified into two groups based on ankle-brachial index (ABI) measurements (ABI ≤ 0.9 n = 43, ABI ≤ 0.5 n = 16). A total of 60 subjects aged 70.4 ± 5.5 years (females n = 42, males n = 18) with ABI > 0.9 constituted a reference group. NPT concentration reached values above 10 nmol/L in patients with PAD, which differed significantly from reference group (8.15 ± 1.33 nmol/L). High levels of CRP > 5 mg/L, TC > 200 mg/dL as well as lipoproteins LDL > 100 mg/dL and non-HDL > 130 mg/dL were found in the same group, indicating the relationship between NPT and conventional atherogenic markers. The endothelial progenitor cells (EPCs) tended toward lower values in patients with ABI ≤ 0.5 when compared to reference group, and inversely correlated with NPT. These findings indicate a crucial role of NPT in atheromatous process and its usefulness in monitoring PAD severity. However, the role of NPT in chronic PAD needs further studies including relatively high number of subjects.

Circulating Mediators of Apoptosis and Inflammation in Aging; Physical Exercise Intervention.

Sarcopenia is an age-related loss of skeletal muscle mass caused by many cellular mechanisms and also by lifestyle factors such as low daily physical activity. In addition, it has been shown that sarcopenia may be associated with inflammation and cognitive impairment in old age. Regular exercise is key in reducing inflammation and preventing sarcopenia and diseases related to cognitive impairment. The study was designed to assess the impact of exercise training on circulating apoptotic and inflammatory markers of sarcopenia in older adults. Eighty older adults aged 70.5 ± 5.8 years were randomized to the physically active group who participated in a 10-month Tai-Chi training session (TC, n = 40) and the control group who participated in health education sessions (HE, n = 40). Tai-Chi training caused a significant decrease in fat mass (FM) by 3.02 ± 3.99%, but an increase in appendicular skeletal muscle mass index (ASMI) by 1.76 ± 3.17% and gait speed by 9.07 ± 11.45%. Tai-Chi training elevated the plasma levels of C-reactive protein (CRP), tumor necrosis factor (TNFα), and tumor necrosis receptor factor II (TNFRII), and decreased caspases 8 and 9. Despite the increase in TNFα, apoptosis was not initiated, i.e., the cell-free DNA level did not change in the TC group. The study demonstrated that Tai-Chi training significantly reduced the symptoms of sarcopenia through the changes in body composition and physical performance, and improvements in cytokine-related mechanisms of apoptosis.

Lifestyle exercise attenuates immunosenescence; flow cytometry analysis.

BACKGROUND: Interaction of physical activity and overall immune profile is very complex and depends on the intensity, duration and frequency of undertaken physical activity, the exposure to cytomegalovirus (CMV) infection and the age-related changes in the immune system. Daily physical activity, which particularly influences immunity, declines dramatically with age. Therefore, the aim of the study was to explain whether physical activity sustained throughout life can attenuate or reverse immunosenescence. METHODS: Ninety-nine older adults (60-90 years) were recruited for the study. According to the 6-min walk test (6WMT), the Åstrand-Ryhming bike test (VO2max) and Community Healthy Activities Model Program for Seniors (CHAMPS) questionnaire, the individuals were classified as physically active (n = 34) and inactive (n = 20) groups. The analysis of T lymphocytes between active vs. inactive participants was performed using eight-parameter flow cytometry. RESULTS: Analysis of the baseline peripheral naïve and memory T lymphocytes showed a significant relationship of lifestyle exercise with the CD4/CD8 ratio. Above 50% of physically active participants demonstrated the CD4/CD8 ratio ≥ 1 or ≤ 2.5 contrary to the inactive group who showed the ratio < 1. The older adults with the result of 6WMT > 1.3 m/s and VO2max > 35 mL/kg/min had a significantly higher CD4+CD45RA+ T lymphocyte percentage and also a higher ratio of CD4+CD45RA+/CD4+CD45RO+. Interestingly, in active older adults with IgG CMV+ (n = 30) the count of CD4+CD45RA+ T lymphocytes was higher than in the inactive group with IgG CMV+ (n = 20). CONCLUSION: Based on the flow cytometry analysis, we concluded that lifestyle exercise could lead to rejuvenation of the immune system by increasing the percentage of naïve T lymphocytes or by reducing the tendency of the inverse CD4/CD8 ratio.

Intermittent Hypoxic Exposure Reduces Endothelial Dysfunction.

Intermittent exposure to hypoxia (IHE) increases the production of reactive oxygen and nitrogen species as well as erythropoietin (EPO), which stimulates the adaptation to intense physical activity. However, several studies suggest a protective effect of moderate hypoxia in cardiovascular disease (CVD) events. The effects of intense physical activity with IHE on oxi-inflammatory mediators and their interaction with conventional CVD risk factors were investigated. Blood samples were collected from elite athletes (control n = 6, IHE n = 6) during a 6-day IHE cycle using hypoxicator GO2 altitude. IHE was held once a day, at least 2 hours after training. In serum, hydrogen peroxide (H2O2), nitric oxide (NO), 3-nitrotyrosine (3-Nitro), proinflammatory cytokines (IL-1ß and TNFα), high sensitivity C-reactive protein (hsCRP), and heat shock protein 27 (HSP27) were determined by the commercial immunoenzyme (ELISA kits) or colorimetric methods. Serum erythropoietin (EPO) level was measured by ELISA kit every day of hypoxia. IHE was found to significantly increase H2O2, NO, and HSP27 but to decrease 3NT concentrations. The changes in 3NT and HSP27 following hypoxia proved to enhance NO bioavailability and endothelial function. In the present study, the oxi-inflammatory mediators IL-1ß and hsCRP increased in IHE group but they did not exceed the reference values. The serum EPO level increased on the 3rd day of IHE, then decreased on 5th day of IHE, and correlated with NO/H2O2 ratio (r s = 0.640, P < 0.05). There were no changes in haematological markers contrary to lipoproteins such as low-density lipoprotein (LDL) and non-high-density lipoprotein (non-HDL) which showed a decreasing trend in response to hypoxic exposure. The study demonstrated that IHE combined with sports activity reduced a risk of endothelial dysfunction and atherogenesis in athletes even though the oxi-inflammatory processes were enhanced. Therefore, 6-day IHE seems to be a potential therapeutic and nonpharmacological method to reduce CVD risk, especially in elite athletes participating in strenuous training.

Lipoxins, RevD1 and 9, 13 HODE as the most important derivatives after an early incident of ischemic stroke.

There is limited information available regarding the association of plasma free fatty acids (FFA) and inflammation mediators with ischemic stroke. At the same time, new treatment strategies are being pursued. The aim of this study was to carry out a thorough analysis of inflammation with multiple FFA-derivative mediators after and ischemic stroke and standard treatment. HPLC separations of 17 eicosanoids were performed using an Agilent Technologies 1,260 liquid chromatograph. The profiles of the esters of fatty acids were labelled by means of gas chromatography. FFA, and eicosanoid profiles in the group of patients after ischemic stroke significantly differed from the profile of the control group. Studies confirmed the involvement of derivative synthesis pathways responsible for the inflammation, especially palmitic acid (9 and 13 HODE), arachidonic acid, EPA and DHA. Arachidonic acid derivatives were synthesised on 5LOX, 15 LOX and COX pathways with the participation of prostaglandins while omega 3 derivatives strengthened the synthesis of resolvins, RevD1 in particular. The ability to accelerate the quenching of inflammation after ischemic stroke seems to be a promising strategy of stroke treatment in its early stage. In this context, our study points to lipoxins, RevD1, and 9, 13 HODE as the most important derivatives.

Intermittent Hypoxic Exposure with High Dose of Arginine Impact on Circulating Mediators of Tissue Regeneration.

Intermittent exposure to hypoxia (IHE) increases production of reactive oxygen and nitrogen species which, as signalling molecules, participate in tissue injury-repair-regeneration cascade. The process is also stimulated by arginine whose bioavailability is a limiting factor for NO synthesis. The effects of IHE in combination with arginine (Arg) intake on myogenesis and angiogenesis mediators were examined in a randomized and placebo-controlled trial. Blood samples were collected from 38 elite athletes on the 1st, 7th and 14th days during the training camp. The oral doses of arginine (2 × 6 g/day) and/or IHE using hypoxicator GO2Altitude (IHE and Arg/IHE) were applied. Serum NO and H2O2 concentrations increased significantly and were related to muscle damage (CK activity >900 IU/mL) in IHE and Arg/IHE compared to placebo. The changes in NO and H2O2 elevated the levels of circulating growth factors such as HGF, IHG-1, PDGFBB, BDNF, VEGF and EPO. Modification of the lipid profile, especially reduced non-HDL, was an additional beneficial effect of hypoxic exposure with arginine intake. Intermittent hypoxic exposure combined with high-dose arginine intake was demonstrated to affect circulating mediators of injury-repair-regeneration. Therefore, a combination of IHE and arginine seems to be a potential therapeutic and non-pharmacological method to modulate the myogenesis and angiogenesis in elite athletes.

Does High Volume of Exercise Training Increase Aseptic Vascular Inflammation in Male Athletes?

Aseptic vascular inflammation can be caused by high levels of various inflammatory and apoptotic factors such as tumor necrosis factor (TNFα), nitric oxide (NO), 3-nitrotyrosine (3-Nitro), and free and oxidized low-density lipoproteins (oxLDL) generated during intense exercise. Endothelial dysfunction resulting from enhanced inflammation has been implicated in cardiovascular disease (CVD). The purpose of the study was to observe the effects of high volume of exercise training on inflammatory mediators and their interaction with conventional CVD risk factors. Blood samples were collected from highly-trained men (n = 16, 21.8 ± 4.0 years) as well as from nonactive men (n = 20, 21.1 ± 1.1 years). NO concentration did not differ between groups while TNFα, 3-Nitro, oxLDL, and CRP levels were significantly higher in athletes compared to nonathletes. TNFα reached even 7-fold higher level in athletes and was highly correlated with CVD risk factor such as TG, lipoproteins LDL and HDL as well as CRP. Approximately 50% of physically active men demonstrated a 20% increase in non-HDL caused by high levels of TC and LDL. These findings suggest that athletes with a high exercise volume demonstrate increased levels of circulating biomarkers of vascular inflammation and may be more likely to have CVD.