Serum Concentrations Of TNF-alpha Research Articles

JAK/STAT signaling in rheumatoid arthritis leukocytes is uncoupled from serum cytokines in a subset of patients

ObjectiveRheumatoid Arthritis (RA) is a systemic autoimmune disease involving pro-inflammatory cytokines that can be therapeutically targeted by antibodies or kinase inhibitors. Nevertheless, these drugs fail in a subset of patients independent of the abundance of the targeted cytokines. We aim to explore the cellular basis of this phenomenon by analyzing the relation of cytokine abundance and activation of downstream signaling pathways in RA. MethodsThe study included 62 RA patients and 9 healthy controls (HC). Phosphorylation of STAT 1–6 in various immune cell subsets was determined ex vivo using a novel robust flow cytometry-based protocol. Serum concentrations of IL-6, IL-10, IL-12p70, IL-17 A, interferon gamma, and TNFα in the same samples were measured using highly sensitive single molecule array (SIMOA). ResultsWe found an increase in circulating cytokines in RA patients, while STAT activity was lower in RA patients compared to HC. Based on STAT activity we determined three endotypes in active RA patients (cDAI>10, n = 28): 1) those with active STAT5a/b signaling in T cells (n = 7/28), 2) those with a low STAT activity in all assessed cell types (n = 14/28), and 3) those with active STAT1 and STAT3 signaling mainly in myeloid cells (n = 7/28). Integrating intracellular STAT activation and cytokine analysis revealed diminished JAK/STAT signaling in a subset of patients (n = 8/20) despite elevated serum cytokine concentrations. ConclusionDiminished JAK/STAT signaling in active RA may partly explain unresponsiveness to therapy targeting cytokine signaling. Analysis of JAK/STAT phosphorylation may identify patients at risk for non-response to these therapies.

Differential effects of heart failure with reduced ejection fraction on locomotor and respiratory muscles

Abstract Background Muscle weakness impairs quality-of-life, exercise capacity, and survival in patients with heart failure and reduced left ventricular ejection fraction (HFrEF). However, the effects on systemic concentrations and local expression of inflammatory cytokines and myokines as well as metabolic markers might differ between locomotor and respiratory muscles. Purpose We prospectively evaluated clinical, functional, and molecular alterations of the diaphragm and the M. vastus lateralis (MVL) from HFrEF patients receiving a left ventricular assist device compared to patients without heart failure undergoing elective coronary bypass grafting (control). Methods Participants (Controls=21, HFrEF=18) underwent cardiopulmonary exercise and respiratory and leg muscle testing. Serum concentrations and local expression of inflammatory cytokines and myokines as well as key enzymes of metabolic pathways were examined in biopsies of the diaphragm and MVL. Results Exercise capacity, respiratory muscle function and endurance force of locomotor muscles were significantly reduced in HFrEF compared with controls (all p<0.05). The serum concentration of Il-6, Il-1beta and TNF-alpha were significantly higher or solely detectable in HFrEF compared with controls. Local mRNA expression of Il-6 was not different in MVL but 2.2-fold higher in the diaphragm of HFrEF compared with controls (p=0.013). In contrast, mRNA expression of Il-6 receptor was significantly reduced by 38% (p=0.004) in MVL of HFrEF compared with controls but comparable in the diaphragm. Serum concentrations of FGF-21 and Musclin were significantly higher in HFrEF compared with controls (all p<0.05). Local mRNA expression of FGF-21 was significantly lower in both MVL and diaphragm of HFrEF compared with controls. FGF-21 receptor 1 mRNA expression was reduced by 18% in the MVL of HFrEF (p=0.02), whereas co-receptor klotho was comparable to controls. In the diaphragm, FGF-21 receptor 1 mRNA expression was comparable between HFrEF and controls, but the co-receptor klotho had a 5-fold higher mRNA expression in HFrEF (p=0.002). We examined the activity of key enzymes of glucose, lipid and ketone metabolism as well as key enzymes of the Krebs cycle. The main differences were found for ß-hydroxyacyl-CoA Dehydrogenase in the diaphragm with a 1.6-fold higher activity in HFrEF compared with controls (p=0.01) and for succinyl-CoA: 3-ketoacid-coenzyme A transferase in the MVL with a 2-fold higher activity in HFrEF compared with controls (p<0.01) indicating a main utilization of lipids in the diaphragm and of ketones in the MVL for energy supply. Conclusions HFrEF induced divergent effects on inflammatory markers, myokine expression and metabolic parameters in locomotor and respiratory muscles in HFrEF patients compared with controls. This indicates that different molecular alterations contribute to locomotor/respiratory muscle dysfunction and reduced whole-body exercise capacity.

Selected adipocytokine concentrations in patients hospitalized for exacerbated chronic heart failure

Introduction: The role of adipose tissue as energy storage and endocrine organ is an area of interest in the treatment of several diseases. This study aimed to to evaluate blood adiponectin (ADP), leptin, tumor necrosis factor type alpha (TNF-alpha) concentrations, and their prognostic value in patients with exacerbated chronic heart failure (CHF). Methods and results: The following were assessed in 64 consecutive patients hospitalized for exacerbated CHF and a control group of 32 age and sex-matched individuals admitted due to life-limiting symptoms of peripheral artery disease: serum leptin, ADP, TNF-alpha concentrations, and body composition determined by bioelectrical impedance analysis. Compared to the control group, CHF patients had significantly higher blood ADP concentrations, a higher ratio of ADP to fat mass expressed as a percentage of body mass, and lower blood TNF-alpha concentrations and ratios of TNF-alpha to the visceral fat level (VFL). Compared to patients who survived, patients with CHF who died during the one-year follow-up had significantly higher values of ADP and higher ratios of ADP to body surface area. In the Cox regression model, blood ADP concentration was the only independent risk factor in respect of all-cause mortality during the one-year follow-up (HR; 95% CI: 1.16; 1.03-1.31). Conclusions: Patients with CHF present dysregulation in the secretion of ADP and TNF-alpha. Increased blood ADP concentration was associated with an increase in one-year all-cause mortality by 16%.

Lung-brain 'cross-talk': systemic propagation of cytokines in the ARDS via the bloodstream using a blood transfusion model does not influence cerebral inflammatory response in pigs.

BackgroundInterorgan cross-talk describes the phenomenon in which a primarily injured organ causes secondary damage to a distant organ. This cross-talk is well known between the lung and brain. One theory suggests that the release and systemic distribution of cytokines via the bloodstream from the primarily affected organ sets in motion proinflammatory cascades in distant organs. In this study, we analysed the role of the systemic distribution of cytokines via the bloodstream in a porcine ARDS model for organ cross-talk and possible inflammatory changes in the brain.MethodsAfter approval of the State and Institutional Animal Care Committee, acute respiratory distress syndrome (ARDS) induction with oleic acid injection was performed in seven animals. Eight hours after ARDS induction, blood (35–40 ml kg–1) was taken from these seven ‘ARDS donor’ pigs. The collected ‘ARDS donor’ blood was transfused into seven healthy ‘ARDS-recipient’ pigs. Three animals served as a control group, and blood from these animals was transfused into three healthy pigs after an appropriate ventilation period. All animals were monitored for 8 h using advanced cardiorespiratory monitoring. Postmortem assessment included cerebral (hippocampal and cortex) mediators of early inflammatory response (IL-6, TNF-alpha, iNOS, sLCN-2), wet-to-dry ratio and lung histology. TNF-alpha serum concentration was measured in all groups.ResultsARDS was successfully induced in the ‘ARDS donor’ group, and serum TNF-alpha levels were elevated compared with the ‘ARDS-recipient’ group. In the ‘ARDS-recipient’ group, neither significant ARDS alterations nor upregulation of inflammatory mediators in the brain tissue were detected after high-volume random allogenic ‘ARDS-blood’ transfusion. The role of the systemic distribution of inflammatory cytokines from one affected organ to another could not be confirmed in this study.

Significance of Vascular Cell Adhesion Molecule-1 and Tumor Necrosis Factor-Alpha in HIV-Infected Patients

Background. The aim of this study was the evaluation of the correlation between VCAM-1 and TNF-alpha serum concentrations and various clinical and laboratory parameters in HIV-infected patients. Methods. All included subjects were patients of the Department of Infectious and Tropical Diseases and Hepatology of the Medical University of Warsaw in Poland in the years 2014–2016. The inclusion criteria were: confirmed HIV infection, Caucasian origin, and age > 18 years old. PCT, CRP, serum HIV-1 RNA, CD4/CD8 T cell count, PCR HCV RNA, HBsAg, VCAM-1, and TNF-alpha were measured. The VCAM-1 and TNF-alpha serum levels were evaluated by ELISA. Results. Seventy-two HIV-infected patients were included (16 women and 56 men: mean age 38.7 years, 66.6% cigarette smokers, 34.7% HCV co-infected HCV, and 27.8% ART-naïve). VCAM-1 concentrations were significantly higher in HIV/HCV co-infected patients than in HIV mono-infected patients (125.6 ± 85.4 vs. 78.4 ± 58.6 ng/mL, p = 0.011) and ART-naïve in comparison to patients on cART (121.9 ± 76.5 vs. 69.4 ± 57.1 ng/mL, p = 0.003). The significant positive correlation between HCV-infection and VCAM-1 and negative correlation between cART use and VCAM-1 was confirmed in multivariate analyses. The only variable associated significantly with TNF-alpha concentration was lymphocytes T CD8+ cell count (p = 0.026, estimate = 0.033). Conclusions. Successful cART and HCV eradication seemed to play an important role in the reduction of endothelial dysfunction and persistent inflammation in HIV-infected patients. CD8 T cell count seemed to be one of the markers of the pro-inflammatory state in HIV-infection patients.

Improvement of Cognitive Function and Interleukin 1 Beta Serum Concentrations Following Cardiac Pacemaker Implantation in Patients with Symptomatic Bradycardia.

Background and aim: Bradyarrhythmias cause a low cerebral blood flow with secondary neuronal ischemia and cognitive dysfunction. This study aims to assess the effect of cardiac pacemaker implantation (PI) on the cognitive function and inflammatory markers (TNF alpha, IL1β). Material and method: We conducted a prospective observational study on a number of 31 patients with symptomatic bradyarrhythmias. We performed the cognitive function assessment by two tests (Mini-Mental State Examination and Trail Making Test A), cardiac output assessment (echocardiographic), and determination of IL 1β and TNF alpha serum concentrations before pacemaker implantation and after an average period of 42 days from pacemaker implantation.Results: After pacemaker implantation we observed an increase in the cardiac index by 0.71 L/min/m2 (p < 0.001) and a better scoring in cognitive performance; the mean MMSE score increased by two points (p < 0.001), and Trail Making Test A had an improvement of 16 s (p < 0.001). Regarding the inflammatory markers, a significant decrease in IL-1β with 8.6 pg/mL (p = 0.049) after pacemaker implantation was observed. Additionally, we found statistically significant correlations between IL1β and TNF alpha (positive correlation, p = 0.005), between the MMSE and cardiac index (p < 0.001), between the Trail Making Test and cardiac index (p = 0.001), and between the MMSE and Trail Making Test (p = 0.003). Conclusions: Our findings suggest that cardiac pacemaker implantation was associated with improved cognitive function—possibly related to an increased cardiac output and with adecreased serum IL1β concentration in subjects with symptomatic bradycardia.

Quantitative Evaluation of the Trauma of CT Navigation PELD and OD in the Treatment of HLDH: A Randomized, Controlled Study

More evidence is required to support that computerized tomography navigation percutaneous spinal endoscopy in the treatment of highly migrated lumbar disc herniation is a more minimally invasive surgery than open discectomy . To quantitatively evaluate the efficacy and minimal invasiveness of computerized tomography navigation percutaneous spinal endoscopy and open discectomy in highly migrated lumbar disc herniation. A prospective randomized study. First Affiliated Hospital of Gannan Medical College. From August 2016 to February 2020, 68 patients with highly migrated lumbar disc herniation had undergone discectomy. Thirty-five of them randomly received computerized tomography (CT) navigation percutaneous spinal endoscopy at the pain department (CT navigation percutaneous spinal endoscopy group), and 33 patients received open discectomy at the orthopedics department (open discectomy group). The Visual Analog Scale (VAS) score, Japanese Orthopaedic Association (JOA) score, and modified MacNab criteria were applied to evaluate the clinical situations pre- and post-operation. The serum concentrations of IL-6, TNF-alpha, creatine phosphokina (CPK), and C-reactive protein (CRP) in the 2 groups were quantitatively measured. The postoperative VAS scores of the back and lower extremity were lower than those pre-operation in both groups, while the VAS score of back pain in the open discectomy group was significantly higher than that in the CT navigation percutaneous spinal endoscopy group at one week post-operation (P < 0.01). The postoperative JOA scores were significantly higher than those pre-operation in both groups. The serum concentrations of IL-6, TNF-alpha, CPK, and CRP in the open discectomy group were higher than those in the computerized tomography navigation percutaneous spinal endoscopy group postoperatively (P < 0.01). This is a single-center randomized study and with the limitation of the sample size. CT navigation percutaneous spinal endoscopy is a more minimally invasive surgery than open discectomy.Certificate number for the medical institution conducting the clinical trials for humans in China: 934.

Serum biomarkers differentiating Kawasaki disease from febrile infections: A pilot case-control study.

Although some serum biomarkers are elevated in both Kawasaki disease (KD) and infections, these conditions have not been compared by individual or combined biomarkers. The aim of this study, undertaken between January 2016 and May 2018 in a large teaching hospital, was to compare the serum concentration of cytokines, metalloproteinases (MMP) and heat shock protein (HSP) between cases defined as children with Kawasaki disease (KD) and those with febrile infections (controls). Serum concentrations of tumour necrosis factor-alpha (TNF-alpha), interleukins (IL 1beta, 6, and 8), heat shock proteins (HSP 60 and 70) and matrix metalloproteinase (MMP 9) were measured on admission in 17 children under six years of age with a temperature >38.5 °C for ≥five days, and compared between the two groups. The median age was 25 months and the median duration of fever eight days. Seven children were diagnosed with KD and ten had a febrile infection. Only the serum concentrations of IL-6 and TNF-alpha were significantly higher in the former than in the latter group (P = 0.01 and 0.04 respectively). To differentiate between the two groups with the best sensitivity and specificity, the optimal cut-off value for IL-6 was 12.6 pg/mL, and for TNF-alpha 47.9 pg/mL. Their combined increase, however, outperformed their individual concentrations. The characteristic diagnostic “signature” of the combined elevation of IL-6 and TNF-alpha serum levels has the potential, in febrile children, to differentiate early KD from febrile infections, allowing the institution of appropriate therapy.

Commentary: Obesity: The “Achilles heel” for COVID-19?

Commentary: Obesity: The “Achilles heel” for COVID-19?

Are adipokines associated with atrial fibrillation in type 2 diabetes?

The potential effect of adipokines on the development of AF is yet to be established. The aim of this study was to investigate the association of baseline serum adipokines with 1) the presence of AF at baseline and 2) future risk of AF development. The current study is a sub-analysis of the prospective, randomised AVOCADO (Aspirin Vs./Or Clopidogrel in Aspirin-resistant Diabetics inflammation Outcomes) trial. The AVOCADO study included patients with type 2 DM burdened with at least two additional cardiovascular risk factors and receiving acetylsalicylic acid. In patients included in the current analysis adipokines and inflammatory biomarker levels were measured. Information on the subsequent AF diagnosis was collected after a median of 5.4 years of follow-up. A total of 273 patients with type 2 DM (median age 68 years; 52% male) were included in the initial analysis comparing patients with and without AF at baseline. Patients with diagnosed AF (12%) had higher levels of serum resistin [8.5 (5.8-10.5) vs. 6.9 (5.6-8.7) ng/mL; p = 0.034], adiponectin [6.9 (5.6-8.7) vs. 2.7 (1.8-4.2) ng/mL; p = 0.032], and N-terminal pro-B-type natriuretic peptide [336 (148-473) vs. 108 [45-217]; p < 0.001) than non-AF patients. There were no significant differences in serum leptin, IL-6, and TNF-alpha concentrations between the two groups. From subjects without known AF at study entry, 19% developed AF at follow-up. In logistic regression analysis, baseline adipokine levels did not predict AF development. In type 2 DM, patients with AF have higher resistin and adiponectin concentrations than patients with no AF. None of the studied adipokines proved a predictor of future AF development.

High serum concentration of dipeptidyl peptidase 4 at early stage of obesity – preliminary study

Background: Adipose tissue has been recognized as an endocrine organ of considerable complexity, able to secrete adipose-derived factors named adipokines. The secretion of adipokines depends greatly on the volume of body fat, which in turn significantly changes their activity towards a diabetogenic, proinflammatory, and atherogenic pattern. One of the discovered adipokines is dipeptidyl peptidase 4 (DPP4).&lt;br&gt;Objectives: The aim of this preliminary study was to establish an association between serum concentration of DPP4 and obesity at early stage.&lt;br&gt;Material and methods: A total of 32 obese adult volunteers and 40 lean controls were studied. Total cholesterol, triglycerides, HDL (high-density lipoprotein), LDL (low-density lipoprotein) and glucose concentrations were assessed in serum/plasma samples by using commercial tests. Body mass index (BMI) and waist-hip ratio (WHR) were determined. Serum concentrations of DPP4, leptin, visfatin, CRP (C-reactive protein), and TNF-alpha (tumor necrosis factor alpha) were measured using commercial ELISA immunoassay tests.&lt;br&gt;Results: Serum concentrations of DPP4, leptin and visfatin were significantly higher in obese than in lean subjects. The concentration of DPP4 positively correlated with BMI and body mass. Serum CRP and TNF-alpha were increased in obese compared to non-obese, and had a positive correlation with BMI, WHR and body mass.&lt;br&gt;Conclusions: We showed that there is an association between the DPP4, leptin and visfatin concentration in serum and elevated body weight and BMI even at early stage of obesity (I stage of obesity). It suggest the importance of adipose tissue reduction to prevent rise of adipokines levels and further negative metabolic and inflammatory changes.

Circulating Wnt1-inducible signaling pathway protein-1 (WISP-1/CCN4) is a novel biomarker of adiposity in subjects with type 2 diabetes.

Wnt1-inducible signaling pathway protein 1, or cellular communication network factor 4 (CCN4), a member of CCN family of secreted, extracellular matrix associated signaling proteins, recently was validated as a novel adipose tissue derived cytokine. To assess the relationships between circulating CCN4, adipose tissue distribution and function, and chronic low-grade inflammation in subjects with type 2 diabetes. We observed 156 patients with type 2 diabetes and 24 healthy controls. Serum levels of CCN4, hsCRP and alpha1-acid glycoprotein (alpha1-AGP) were measured by ELISA. Serum concentrations of leptin, resistin, visfatin, adipsin, adiponectin, IL-6, IL-8, IL-18 and TNF-alpha were determined by multiplex analysis. Fat mass and distribution was assessed by DEXA. Mean diameter of adipocytes was estimated in samples of subcutaneous adipose tissue. Patients with diabetes had higher levels of circulating CCN4, leptin, resistin, adipsin, visfatin, hsCRP, alpha1-AGP, and IL-6 (all p<0.02). The CCN4 concentration correlated positively with percentage of fat mass in central abdominal area, as well as with leptin, resistin and visfatin levels; negative correlation was found between CCN4 and mean adipocyte diameter. In multiple regression analysis fat mass in central abdominal area was independent predictor for CCN4 concentration. In subjects with type 2 diabetes serum levels of CCN4 are associated with central abdominal fat mass and adipose tissue dysfunction.

Functional ability of neutrophils in patients with ischemic heart disease

Purpose. The study of protein-producing and lipid-releasing ability of neutrophils and its clinical significance in patients with IHD.Materials and methods. 25 patients with arterial hypertension without clinical and ultrasound manifestations of atherosclerosis were examined; 47 patients with coronary artery disease with stable angina, as well as 19 patients with unstable primary angina. The comparison group — 33 healthy persons. In the serum, enzyme-linked immunosorbent assay was used to evaluate the concentration of C-reactive protein (CRP), lipoprotein a (LPa), VII coagulation factor VII (VIIf), defensins-alpha (1–3), interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor alpha (TNF-alpha). Leukocytes, predominantly represented by neutrophils, which were further cultivated, were excreted from peripheral blood in the presence of dextrans; the levels of CRP, LPa, defensins-alpha (1–3), VIIf, and lipid-releasing ability of leukocytes (LRAL) were assessed according to the method of A. V. Tuev and V. Yu. Mishlanov. An angiographic study, duplex scanning arteries, and echocardiography were performed.Results. It has been established that in patients at the stage of preclinical atherosclerotic lesion, the ability of leukocytes to form protein-lipid complexes (PLC), marked by LRAL, practically does not differ from healthy individuals, but already at this stage of atherogenesis an increase in their ability to produce antimicrobial peptides — defensins-alpha (1–3). In patients with coronary artery disease with stable angina pectoris, an increase in leukocyte production of a wide range of proteins — defensins-alpha (1–3), VIIf, LPA and CRP in combination with signs of a systemic inflammatory reaction, marked by high concentrations of CRP, interleukin-6 and tumor necrosis factor alpha in serum, was noticed. At this stage of atherogenesis, the value of LRAL is significantly different from the values of healthy individuals. It is shown that the higher the LRAL value, the higher the functional class of chronic heart failure in these patients (R = 0.4; p = 0.02). In patients with coronary artery disease with primary unstable angina, the maximum LRAL value was detected, and in patients with ultrasound signs of plaque instability, high concentrations of CRP in neutrophilic supernatants were found. Correlation analysis revealed that, in patients with coronary artery disease, the average percentage of coronary artery stenosis, according to angiography, is directly related to the LRAL value (R = 0.7; p = 0.03) and the serum concentration of TNF-alpha (R = 0.5; p = 0.03), and the number of clinically significant stenoses — with the magnitude of LRAL (R = 0.4; p = 0.04) and the concentration in supernatants VIIf (R = 0.5; p = 0.04).Conclusion. The LRAL value, CRP and defensin-alpha content in leukocyte supernatants in IHD patients are interconnected with the severity and activity of atherosclerotic lesion of arteries, which is confirmed by the results of examination of patients at the stage of preclinical, clinically manifest stable and unstable atherosclerotic lesion.

FOXP3+ T-REGULATORY LYMPHOCYTES IN HYPERTENSIVE PATIENTS

Objective: Development of coronary atherosclerosis in patients with arterial hypertension (AH) is associated with the state of chronic low-grade inflammation, but the role and function of T-regulatory (Treg) lymphocytes in this process is not yet fully elucidated. Design and method: In total 24 patients with AH of high and very high cardiovascular risk (8 men and 16 women; 61.0 (55.5; 64.00) y.o.) have been recruited in the study. All the patients underwent coronary angiography to verify the presence of coronary stenosis. Among all the recruited patients 16 individuals were characterized by at least 50% coronary stenosis. Numbers of Treg-lymphocytes were evaluated by flow cytometry according to the expression of CD4, CD25 and FoxP3 molecules. Concentrations of high-sensitive C-reactive protein (hsCRP) were measured by ELISA. Concentrations of inflammatory and anti-inflammatory cytokines were evaluated in serum and in supernatants of intact and lipopolysaccharide (LPS)-stimulated peripheral blood mononuclear cells’ culture by multiplex analysis. Results: Patients with coronary stenosis higher than 50% (Gr. 1) were characterized by elevated numbers of CD4+FoxP3+ Treg lymphocytes compared to the patients with minor coronary changes (Gr. 2) (3.67 (2.61; 5.37) % vs. 2.33 (1.56; 3.68) %; p = 0.047), as well as by elevated inflammatory markers, such as hsCRP (6.24 (1.98; 6.95) mg/l in Gr. 1 vs. 1.79 (1.32; 2.51) mg/l in Gr. 2; p = 0.066) and LPS-stimulated secretion of TNF-alpha (9126 (6908; 14108) pg/ml in Gr. 1 vs. 2517 (2512; 6198) pg/ml in Gr. 2; p = 0,030). Both parameters are typical to the chronic low-grade inflammation. In total group of patients concentration of serum TNF-alpha was directly related to the concentration of fasting and postprandial glucose (Rs = 0,536; p = 0,032 and Rs = 0,726; p = 0,001, respectively) as well as to the levels of HbA1c (Rs = 0,588; p = 0,035). We have revealed inverse relationships between numbers of CD25hiFoxP3+ Treg-lymphocytes and fasting levels of insulin (Rs = -0,565; p = 0,035) and HOMA (Rs = -0,666; p = 0,009). Conclusions: We have revealed the increase of Treg-lymphocytes’ numbers in patients characterized with 50% stenosis of coronary arteries, which may have compensatory role to counterbalance the state of the chronic low-grade inflammation and may be associated with the poor glycemic control in these patients.

Serum levels of TNF-alpha in patients with chronic schizophrenia during treatment augmentation with sarcosine (results of the PULSAR study)

Sarcosine, glycine transporter inhibitor, increases glycine levels around NMDA receptor, improving primary negative symptoms of schizophrenia. The aim of our study was to find a potential relationship between initial TNF-alpha level, its changes and schizophrenia symptoms severity, resulting from adding sarcosine to a stable antipsychotic treatment. Sixty subjects with stable schizophrenia were randomized to receive either 2 g of sarcosine or placebo and completed a 6-month, double blind, placebo-controlled study. Three patients on sarcosine and one taking placebo did not complete TNF-alpha tests, planned at the beginning, after 6 weeks and after 6 months. For clinical assessments we used PANSS and CDSS scales. No changes in TNF-alpha serum concentrations in both groups at any time-points was noted. The sarcosine group achieved significant improvement in negative symptoms, general psychopathology and total PANSS score group, however without any significant correlations between TNF-alpha levels and PANSS scores in all assessments. Positive correlations between TNF-alpha levels and CDSS score were found in the placebo group and total study group. Initial TNF-alpha concentrations cannot be used as a predictor of the improvement resulting from adding sarcosine. Sarcosine does not significantly affect TNF-alpha levels. TNF-alpha may be involved in mechanisms related to depressive symptomatology in schizophrenia.

Circulating levels of interleukin-17A, tumor necrosis factor-alpha, interleukin-18, interleukin-10, and cognitive performance of patients with relapsing-remitting multiple sclerosis

Multiple sclerosis (MS) is associated with cytokine imbalance and high rate (40–70%) of cognitive impairment.The objective of this study is to investigate the relationship between serum concentrations of tumor necrosis factor (TNF)-alpha, interleukin (IL)-17A, IL-18, IL-10, and cognitive performance in patients with relapsing-remitting MS (RRMS).MethodsThe study comprised 159 patients with RRMS (mean age 40.08 ± 8.48 years) in remission phase and 86 age-, gender-, and education-matched healthy controls. Paced Auditory Serial Addition Test (PASAT), Symbol Digit Modalities test (SDMT), and Isaacs test were used for assessment of working memory, attention, visuo-perceptual abilities, information processing speed, and executive functions. Serum cytokine concentrations were measured by enzyme-linked immunosorbent assay (ELISA).ResultsPatients had significantly increased serum concentrations of TNF-alpha and IL-17A and decreased levels of IL-10 compared to the controls (p < 0.05). Negative correlation was found between serum TNF-alpha and SDMT score in patients with disease evolution longer than 10 years (rxy = −0.258 p = 0.033); PASAT and SDMT scores were in negative correlation with concentration of IL-17A (rxy = −0.229 p = 0.004; rxy = −0.166 p = 0.041). Cognitive impairment was established in 46.5% (n = 74) of the patients. Cognitively impaired patients had significantly higher serum IL-17A than cognitively preserved individuals (p = 0.007). Multiple linear regression analysis revealed IL-17A as a significant predictor of cognitive performance in RRMS patients.ConclusionThe results from this study suggest that pro-inflammatory cytokines IL-17A and TNF-alpha simultaneously with decreased IL-10 are involved in cognitive deterioration in RRMS.

Relationship between etanercept and thyroid function in patients with psoriasis vulgaris.

Background and aimPsoriasis vulgaris, a chronic inflammatory skin disease, requires a long term medication, in order to avoid relapsing episodes. TNF-alpha, one of the targeted molecule in psoriasis therapy, seems to be also involved in thyroid disorders etiopathogenesis. The aim of this study was to evaluate the relationship between anti TNF-alpha therapy and thyroid parameters: serum level of triiodothyronine (T3), free thyroxine (FT4), thyroid-stimulating hormone (TSH) and antithyroidperoxidase antibody (AbTPO) in psoriasis treated population.MethodsThe study was performed on 44 patients with psoriasis vulgaris (20 patients under antiTNF-alpha treatment (etanercept), 24 patients with no previous systemic therapy). Serum concentrations of hormones, AbAntiTPO and TNF-alpha were measured and a thyroid ultrasonographic evaluation was performed for each patient.ResultsThe mean serum level of FT4 was significantly higher in patients with no systemic treatment (p<0.05). The patients treated with etanercept had a significantly higher level of TNF-alpha (p<0.05). No significant difference was observed for the other evaluated parameters. Also, we found a significant negative correlation between TNF-alpha and TSH levels (r=−0.366, p=0.015).ConclusionsWe only found that the mean level of FT4 was significantly higher in patients with no systemic treatment. Also, a negative strong correlation was seen between serum level of TSH and TNF-alpha. Based on our data, comparison with other anti TNF-alpha therapies might be of interest in future studies.

Repeated Measurements of Serum Concentrations of TNF-alpha, Interleukin-6, and Interleukin-10 in the Evaluation of Internal Carotid Artery Stenosis Progression

Long-term trends in serum concentrations of IL-6 and IL-10 in patients with ICA stenosis helps predict stenosis progression and unfavorable changes in plaque morphology.

Repeated measurements of serum concentrations of TNF-alpha, interleukin-6 and interleukin-10 in the evaluation of internal carotid artery stenosis progression

Background and aimsThe inflammatory process (with TNFα, interleukin-6 and interleukin-10 involvement) plays a key role in the development, progression and destabilization of atherosclerotic plaques. The aim of this study was to assess the importance of double-checked measurements of TNFα, interleukin-6 (IL-6) and interleukin-10 (Il-10) serum levels in patients with internal carotid artery (ICA) stenosis to determine the dynamics of changes in the stenosis degree and in the ultrasound plaque morphology. MethodsThe study included 65 patients with ICA stenosis. Ultrasound of the carotid arteries was performed during qualification and every 3 months to identify any progression of stenosis degree and dynamics of changes in plaque morphology.Serum concentrations of TNF-alpha, IL-6 and IL-10 were measured during qualification and at month 6 of the study. Calculations considered cytokine concentrations and their indices determined as relative differences of cytokine levels assessed in the first and in second tests. ResultsPatients with increasing degree of ICA stenosis had higher indices of IL-6 and IL-10 than patients without any increase in the stenosis degree. In patients with unfavorable dynamics of changes in plaque morphology, significantly higher levels of interleukin-6 were found in the second test; these patients had higher indices of IL-6 and IL-10 than patients with favorable dynamics of atherosclerotic plaque morphology on ultrasound. ConclusionsLong-term trends in serum concentrations of IL-6 and IL-10 in patients with ICA stenosis allow to predict the progression of the degree of stenosis and the unfavorable change of atherosclerotic plaque morphology.

Serum and peritoneal fluid concentrations of soluble human leukocyte antigen, tumor necrosis factor alpha and interleukin 10 in patients with selected ovarian pathologies

BackgroundAlthough immune system plays a key role in the pathogenesis of both endometriosis and ovarian cancer, its function is different. Therefore, we hypothesized, that selected immune parameters can serve as diagnostic markers of these two conditions. The aim of this study was to compare serum and peritoneal fluid concentrations of sHLA-G, IL-10 and TNF-alpha in women with selected ovarian pathologies: benign serous cysts, endometrioma and malignant tumors. Clinical significance of using them for diagnostic purposes in women with serous ovarian cysts, endometriosis, and ovarian cancer, which in the future may improve the early diagnosis of ovarian diseases.Case PresentationThe study included women treated surgically for benign serous ovarian cysts, ovarian endometrioma and serous ovarian adenocarcinomas. Peripheral blood and peritoneal fluid samples were obtained intraoperatively. Patients with benign serous cysts, endometrioma and ovarian malignancies did not differ significantly in terms of their serum and peritoneal fluid concentrations of sHLA-G. Ovarian cancer patients presented with significantly higher median serum concentrations of IL-10 and TNF-alpha than other study subjects. Median concentrations of IL-10 and TNF-alpha in peritoneal fluid turned out to be the highest in ovarian cancer patients, followed by women with endometrioma and subjects with benign serous cysts. All these intergroup differences were statistically significant. Irrespective of the group, median concentrations of sHLA-G, IL-10 and TNF-alpha in peritoneal fluid were higher than serum levels of these markers.ConclusionsElevated serum and peritoneal fluid concentrations of IL-10 and TNF-alpha distinguish ovarian malignancies and endometriomas from benign serous ovarian cysts. In contrast to endometriosis, ovarian malignancies are characterized by elevated peritoneal fluid concentrations of IL-10 and TNF-alpha, elevated serum concentrations of IL-10 and low serum levels of TNF-alpha. Serum and peritoneal fluid concentrations of sHLA-G have no diagnostic value in differentiating between ovarian malignancies and endometriomas.