sTNFR1 Levels Research Articles

Soluble Tumor Necrosis Factor Receptor Type 1 Levels Exhibit A Stronger Association With Renal Outcomes Than Traditional Risk Factors in Chinese Subjects With Type 2 Diabetes Mellitus

Objective: Associations between albuminuria and renal outcomes are inconsistent in patients with type 2 diabetes (T2D). Soluble tumor necrosis factor receptor type 1 (sTNFR1) is involved in declined kidney function and poor renal outcomes but this has not been confirmed among Chinese T2D patients. This study aimed to examine the association of sTNFR1 and renal outcomes in a cohort of these patients.Methods: Two hundred and eighty-three Chinese T2D patients were enrolled in a prospective observational study which excluded individuals with estimated glomerular filtration rates (eGFR) <30 mL/min/1.73m2. Composite renal outcomes included either or both a >30% decline in eGFR and worsening albuminuria from consecutive tests of blood/urine during a 3.5-year follow-up.Results: Higher sTNFR1 levels were associated with impaired renal outcomes. sTNFR1 levels of ≥979 pg/mL yielded the most sensitivity and specific predictions of renal outcomes according to the receiver operating curve (area under the curve 0.68, P<.001; sensitivity 78.3%, specificity 48.9%). Renal events occurred more frequently in subjects with sTNFR1 ≥979 pg/mL than in others (sTNFR1 <979 pg/mL; 29% versus 10%; P<.001 by log-rank test). The association between sTNFR1 ≥979 pg/mL and renal outcomes remained significant after adjustment for relevant covariates (adjusted hazard ratio 2.43, 95% confidence interval 1.18 to 5.02; P = .01) and consistent across subgroups stratified by age, sex, blood pressure, eGFR, albuminuria, and the use of renin-angiotensin system inhibitors.Conclusion: Increased sTNFR1 levels were associated with renal outcomes in Chinese T2D subjects, making sTNFR1 a potential biomarker in diabetic kidney disease.

N-acetylcysteine as an adjunctive treatment for smoking cessation: a randomized clinical trial.

Objective:This randomized controlled trial examined the efficacy and safety of N-acetylcysteine as an adjunctive treatment for smoking cessation.Methods:Heavy smokers were recruited from smoking cessation treatment for this 12- week randomized controlled trial. Eligible tobacco use disorder outpatients (n=34) were randomized to N-acetylcysteine or placebo plus first-line treatment. Abstinence was verified by exhaled carbon monoxide (COexh). The assessment scales included the Fagerström Test for Nicotine Dependence, the Hamilton Depression Rating Scale, the Hamilton Anxiety Rating Scale, the Minnesota Nicotine Withdrawal Scale, and the Medication Adherence Rating Scale. We also assessed anthropometrics, blood pressure, lipid profile, and soluble tumor necrosis factor receptor (sTNF-R) levels 1 and 2.Results:First-line treatment for smoking cessation plus adjunctive N-acetylcysteine or placebo significantly reduced COexh (p < 0.01). In the N-acetylcysteine group, no significant changes were found in nicotine withdrawal symptoms, depressive and anxiety symptoms, anthropometric measures, blood pressure, or glucose compared to placebo. However, there was a significant reduction in sTNF-R2 levels between baseline and week 12 in the N-acetylcysteine group.Conclusions:These findings highlight the need to associate N-acetylcysteine with first-line treatment for smoking cessation, since combined treatment may affect inflammation and metabolism components.Clinical trial registration:NCT02420418

Serum soluble tumor necrosis factor receptor (sTNFR) 1 and 2 in STEMI

Tumor necrosis factor-α (TNF-α) interacts with two soluble receptors: TNFR1 and TNFR2. Little is known about the role of sTNFR1 and sTNFR2 in patients with acute ST-segment elevation myocardial infarction (STEMI). Our hypothesis was that the serum levels of sTNFR1 and sTNFR2 might be a marker of the severity of STEMI. We prospectively enrolled 230 consecutive STEMI patients who underwent PCI revascularization in our hospital into a prospective cohort. Blood samples were collected at 5 time points: admission, 4, 24, 48 hours and 1 month after admission (H4, H24, H48, M1). sTNFR1 and sTNFR2 serum levels were assessed using an ELISA assay. Patients underwent cardiac magnetic resonance imaging at M1. Clinical outcomes were recorded over 18 months after STEMI. Mean age of the study population was 59 ± 12 years and 48.5% patients exhibited anterior STEMI. sTNFR1 level significantly increased at H24 with a median of 601.2 pg/mL (interquartile range [IQR] [397.1–896.7]). sTNFR2 level significantly increased at H48 with a median of 2262.3 pg/mL (IQR [1659.6–2862.4]). Patients with sTNFR1 and sTNFR2 peak levels greater than the population median value displayed significantly larger final infarct size and lower LVEF. Patients with peak levels of sTNFR1 and sTNFR2 higher than the population median value were more likely to have an adverse clinical event (MI, stroke, hospitalization for heart failure and all-cause death) during the first 18 months after STEMI (hazard ratio [HR] at 9.0 [3.7–22.2], P = 0.0003 for sTNFR1 and 5.5 [2.1–14.3], P = 0.002 for sTNFR2). Patients with high level of both sTNRF1 and sTNFR2 were at higher risk of adverse clinical event compared to patients with low level (HR = 13.1 [4.4–38.7], P = 0.0005). High levels of circulating sTNFR1 and sTNFR2 were associated with larger infarct size, impaired recovery of LVEF and adverse clinical event in STEMI patients. sTNFR1 and 2 might be useful prognosis markers.

Characterization of the Inflammatory Response to Severe COVID-19 Illness.

Rationale: Coronavirus disease (COVID-19) is a global threat to health. Its inflammatory characteristics are incompletely understood.Objectives: To define the cytokine profile of COVID-19 and to identify evidence of immunometabolic alterations in those with severe illness.Methods: Levels of IL-1β, IL-6, IL-8, IL-10, and sTNFR1 (soluble tumor necrosis factor receptor 1) were assessed in plasma from healthy volunteers, hospitalized but stable patients with COVID-19 (COVIDstable patients), patients with COVID-19 requiring ICU admission (COVIDICU patients), and patients with severe community-acquired pneumonia requiring ICU support (CAPICU patients). Immunometabolic markers were measured in circulating neutrophils from patients with severe COVID-19. The acute phase response of AAT (alpha-1 antitrypsin) to COVID-19 was also evaluated.Measurements and Main Results: IL-1β, IL-6, IL-8, and sTNFR1 were all increased in patients with COVID-19. COVIDICU patients could be clearly differentiated from COVIDstable patients, and demonstrated higher levels of IL-1β, IL-6, and sTNFR1 but lower IL-10 than CAPICU patients. COVID-19 neutrophils displayed altered immunometabolism, with increased cytosolic PKM2 (pyruvate kinase M2), phosphorylated PKM2, HIF-1α (hypoxia-inducible factor-1α), and lactate. The production and sialylation of AAT increased in COVID-19, but this antiinflammatory response was overwhelmed in severe illness, with the IL-6:AAT ratio markedly higher in patients requiring ICU admission (P < 0.0001). In critically unwell patients with COVID-19, increases in IL-6:AAT predicted prolonged ICU stay and mortality, whereas improvement in IL-6:AAT was associated with clinical resolution (P < 0.0001).Conclusions: The COVID-19 cytokinemia is distinct from that of other types of pneumonia, leading to organ failure and ICU need. Neutrophils undergo immunometabolic reprogramming in severe COVID-19 illness. Cytokine ratios may predict outcomes in this population.

Cannabis Use Is Associated With Increased Levels of Soluble gp130 in Schizophrenia but Not in Bipolar Disorder.

The complex effects of plant cannabinoids on human physiology is not yet fully understood, but include a wide spectrum of effects on immune modulation. The immune system and its inflammatory effector pathways are recently emerging as possible causative factors in psychotic disorders. The present study aimed to investigate whether self-administered Cannabis use was associated with changes in circulating immune and neuroendocrine markers in schizophrenia (SCZ) and bipolar disorder (BD) patients. A screening of 13 plasma markers reflecting different inflammatory pathways was performed in SCZ (n = 401) and BD patients (n = 242) after subdividing each group into Cannabis user and non-user subgroups. We found that i) soluble gp130 (sgp130) concentrations were significantly elevated among Cannabis users in the SCZ group (p = 0.002) after multiple testing correction, but not in BD. ii) Nominally significant differences were observed in the levels of IL-1RA (p = 0.0059), YKL40 (p = 0.0069), CatS (p = 0.013), sTNFR1 (p = 0.031), and BDNF (p = 0.020), where these factors exhibited higher plasma levels in Cannabis user SCZ patients than in non-users. iii) These differences in systemic levels were not reflected by altered mRNA expression of genes encoding sgp130, IL-1RA, YKL40, CatS, sTNFR1, and BDNF in whole blood. Our results show that Cannabis self-administration is associated with markedly higher sgp130 levels in SCZ, but not in BD, and that this phenomenon is independent of the modulation of peripheral immune cells. These findings warrant further investigation into the potential IL-6 trans-signaling modulatory, anti-inflammatory, neuroimmune, and biobehavioral-cognitive effects of Cannabis use in SCZ.

Serum concentrations of TNF-α and its soluble receptors in Graves' disease.

Graves’ disease (GD), an organ-specific autoimmune disease, is the most common cause of hyperthyroidism. Tumour necrosis factor-alpha (TNF-α) exhibits immunological and metabolic activities involved in the induction and maintenance of immune responses. We attempted to evaluate the relationship between GD and serum TNF-α and its soluble receptors (sTNFRs), soluble TNF receptor 1 and 2 (sTNF-R1 and sTNF-R2). A total of 72 GD patients and 72 matched healthy individuals were recruited for this study. Serum TNF-α and sTNFRs were measured by sandwich ELISA. In our study, no significant difference was observed in TNF-α, but sTNFRs were found to be significantly elevated in GD patients compared to healthy individuals. Serum sTNFR levels were positively correlated with free triiodothyronine (FT3) and free thyroxine (FT4), and TNF-α was negatively correlated with thyroid-stimulating hormone (TSH) in the GD group. It was also shown that thyrotropin receptor antibody (TRAb) was positively correlated with TNF-α and sTNFRs. Spearman’s correlation analysis showed that only sTNF-R1 was positively correlated with complement C3. Multiple linear regression analysis suggests that serum levels of sTNF-R1 and FT4 may play an important role in the serum level of FT3. According to the median value of FT3 level, GD patients were further divided into a high FT3 group and a low FT3 group. The serum levels of sTNF-R1 in the high FT3 GD group were significantly higher than those in the low FT3 GD group. In conclusion, sTNFRs may play an important role in anti-inflammatory and immune response in GD.

Leptin mediates improvements in cognitive function following treatment with infliximab in adults with bipolar depression

A potential role for leptin in the pathophysiology of bipolar disorder (BD) has been proposed. We recently investigated the effects of the tumor necrosis factor-alpha (TNF-α) antagonist infliximab in individuals with bipolar depression. Leptin is known to interact with the TNF-α system. Herein, we aimed to explore infliximab’s effects on leptin and its relationship with brain structure and function. Sixty adults with bipolar depression were enrolled in this randomized, double-blind, 12-week clinical trial of adjunctive infliximab (n = 29) and saline control (n = 31), which were administered intravenously at weeks 0, 2, and 6. Plasma concentrations of leptin, TNF-α and soluble TNF receptors (sTNFR) 1 and 2 were assessed at weeks 0, 2, 6, and 12. We observed a significant decrease in leptin levels in infliximab-treated patients, relative to placebo. Infliximab treatment also significantly reduced TNF-α and sTNFR2, but not sTNFR1 levels. Changes in sTNR2 levels at week 6 significantly determined changes in leptin at week 12 in infliximab-, but not placebo-treated participants. Improvements in verbal memory and increases in global cortical volume were associated with reduction in leptin levels in the treatment group. Mediation analysis indicated that cognitive improvement in infliximab-treated patients was mediated by reductions in leptin levels, which in its turn were determined by decreases in sTNR2 levels. In conclusion, infliximab treatment reduced plasma leptin levels in individuals with BD, through modulation of sTNFR2. Decreases in leptin signaling were associated with an increase in global cortical volume and better performance in a verbal memory task.

The health outcomes of inflammation and obesity in patients with heart failure

BackgroundAlthough obesity is a risk factor for cardiovascular disease, higher body mass index is related to longer event-free survival in patients with heart failure (HF). While previous research demonstrated that higher levels of inflammatory mediators were associated with shorter event-free survival, the effect of inflammation on the association between obesity and outcomes of HF have not been considered. HypothesisBased on the obesity paradox, we hypothesized that patients with higher baseline body mass index (BMI) would experience better event-free survival than those with lower BMI regardless of inflammatory status. MethodA sample of 415 patients with HF (age 61 ± 11.5 years; 31% female) provided blood to measure soluble tumor necrosis factor receptor1 (sTNFR1), a biomarker of inflammation. Patients were divided into 4 groups based on BMI and a median split of sTNFR1 levels: (1) high BMI ≥ 30 and sTNFR1 > 1804 pg/ml, (2) high BMI ≥ 30 and low sTNFR1 ≤ 1804 pg/ml, and (3) low BMI < 30 and high sTNFR1 > 1804 pg/ml vs. (4) low BMI < 30 and sTNFR1 ≤ 1804 pg/ml. Patients were followed for an average of 365 days to determine the time to first event of either all-cause hospitalization or death. ResultsThere were 177 patients (43%) who experienced either an all-cause hospitalization or death. In a Cox regression, high BMI and high sTNFR1 category predicted time to event (hazard ratio = 1.7, 95% confidence interval = 1.01–2.9) with age, gender, race, left ventricular ejection fraction, New York Heart Association functional class (I/II versus III/IV), log-transformed N-terminal Pro-B-type natriuretic peptide levels, prescribed statin (yes/no), and comorbidity as covariates. ConclusionBeing in a higher inflammation group was associated with shorter event-free survival regardless of BMI. This study provides evidence that inflammation is an important consideration in the association between obesity and better outcomes in patients with HF.

Sex-specific associations of inflammation markers with cognitive decline.

Inflammation is implicated in cognitive decline; however, there is a paucity of data for African American populations and for sex-specific associations. Prospective cohort study. Genetic Epidemiology Network of Arteriopathy/Genetics of Microangiopathic Brain Injury studies. African-American sibships (N=1010). Neurocognitive tests assessed global cognition and four cognitive domains: processing speed, memory, language, and executive function at two time points over seven years. Circulating levels of C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor receptor (TNFR)-1 and TNFR2 were measured at study baseline. Linear mixed models were used to investigate the association between inflammation markers and cognitive decline. Among men, a one SD increase in CRP was associated with an increased rate of decline over 7years in global cognitive Z-score (adjusted difference in slopes=-0.31, p=0.006) and in processing speed Z-score (adjusted difference in slopes=-0.10, p=0.02), but not declines in memory, language, or executive function Z-scores. Also among men, a one SD increase in IL-6 was associated with an increased decline rate in global cognitive Z-score (adjusted difference in slopes=-0.33, p=0.002) and in processing speed Z-score (adjusted difference in slopes=-0.12, p=0.007). There was no difference in decline rates by CRP or IL-6 level in adjusted analyses among women for any cognitive scores. Among men and women combined, a one SD increase in baseline sTNFR1 was associated with a faster rate of decline in memory Z-score (adjusted difference in slopes=-0.09, p=0.02). Baseline sTNFR2 levels did not significantly predict rate of cognitive decline in any cognitive domains. Circulating markers of CRP and IL-6 may be differential risk factors for men and women in relation to cognitive decline. A novel inflammation marker, sTNFR1, may be a useful predictor of memory decline in older adults.

Significant Induction of Soluble TNFR2 Compared with TNFR1 in Serum Samples of HIV Patients with or without Antiretroviral Medication.

Tumor necrosis factor and its receptors (sTNFR1 and sTNFR2) have been implicated in many infectious diseases. Identification of the key receptor (sTNFR1 or sTNFR2) which drives the immunopathogenesis of HIV infection is crucial in developing adjunctive therapy for HIV. This study determined the expression levels of sTNFR1 and sTNFR2 in antiretroviral therapy (ART) - experienced and naïve HIV patients. A total of 40 HIV patients comprising 30 with ART and 10 without ART were enrolled from the Pantang Hospital located in the Greater Accra Region of Ghana for data and blood collection. Serum concentrations of sTNFR1 and sTNFR2 were determined by ELISA. Mann- Whitney U test was used to examine differences in serum levels of sTNFR1 and sTNFR2 between patients on ART and ART naïve patients. Wilcoxon Signed-Rank test was performed to determine the difference between sTNFR1 and sTNFR2, and Kruskal Wallis test was conducted to compare the effect of different antiretroviral drugs on the levels of sTNFR1 and sTNFR2. P< 0.05 was considered statistically significant. A Wilcoxon Signed-Ranks Test indicated serum levels of sTNFR2 was statistically significantly higher than sTNFR1 (Z=-5.51; p<0.001). Levels of sTNFR1 and sTNFR2 did not differ by ART status U =91.00 (Z = -1.84), p = 0.065 and U = 131.50 (Z = -0.58, p =0.560), respectively. There were not significant differences in levels of TNFR2 H(2) = 1.86, p=0.395 and sTNFR1 (H (2) = 4.37, p=0.113 across different ART combinations. Compared to sTNFR1, the level of sTNFR2 is significantly increased during HIV infection irrespective of ART status. The high sTNFR2 level is not associated with antiretroviral drugs and may be another potential target for therapeutic development. This is the first study of sTNFRs in African population.

Effect of acupuncture on patients with cancer-related fatigue and serum levels of CRP, IL-6, TNF-α and sTNF-R1

To observe the therapeutic effect of acupuncture on cancer-related fatigue (CRF) and to explore its possible mechanism. A total of 80 patients with CRF were randomized into an observation group and a control group, and finally 67 patients completed the trial (36 patients in the observation group, 31 patients in the control group). Patients in the control group were treated with conventional chemoradiotherapy and symptomatic treatment, while no particular anti-fatigue intervention was adopted. On the basis of treatment in the control group, acupuncture was applied at Baihui (GV 20), Guanyuan (CV 4), Qihai (CV 6), Fengchi (GB 20), Zusanli (ST 36), Sanyinjiao (SP 6) in the observation group, once a day, 5 times as one course, with 2 days interval between each course, totally 4 courses were required. Before and after treatment, scores of functional assessment of cancer therapy-fatigue (FACT-F) in Chinese and McGill quality of life questionnaire (MQOL), serum levels of C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-α(TNF-α) and soluble TNF receptor-1 (sTNF-R1) were observed in the two groups. ①Compared before treatment, the FACT-F score was decreased after treatment in the observation group (P<0.05), while there was no significant difference in the control group (P<0.05). The change of the FACT-F score in the observation group was larger than that in the control group (P<0.05). ②In the observation group, scores of physiological and psychological dimension were decreased (P<0.05), score of social support dimension was increased after the treatment (P<0.05). The score changes of physiological, psychological and social support dimension in the observation group were larger than those in the control group (all P<0.05). ③After treatment, the serum levels of IL-6, TNF-α and sTNF-R1 were decreased in the observation group (P<0.05), while the serum levels of CPR and IL-6 were increased in the control group (P<0.05). The serum levels of CPR, IL-6 and TNF-α in the observation were lower than those in the control group (P<0.05). ①Acupuncture can improve the related symptoms of depression, weakness and headache in patients with CRF, strengthen their cognition of the support from society and family, and boost the confidence in curing the disease. ②Acupuncture can effectively down-regulate serum levels of the relative inflammatory factors, which may be its possible mechanism on treating CRF.

Efficacy of adjunctive infliximab vs. placebo in the treatment of anhedonia in bipolar I/II depression

We investigated the efficacy of tumour necrosis factor (TNF)-α antagonist infliximab on a measure of anhedonia amongst individuals with bipolar I/II depression (ClinicalTrials.gov identifier NCT02363738). Adults (ages 18–65) with bipolar I/II disorder currently experiencing a major depressive episode with a higher probability of inflammatory activity (i.e., meeting one or more of the following inflammatory/metabolic criteria: obesity and dyslipidemia/hypertension, daily cigarette smoking, diabetes mellitus, migraine, inflammatory bowel disease, and/or C-reactive protein level of ⩾5 mg/L) were enrolled in a double-blind, 12-week clinical trial of adjunctive infliximab (5 mg/kg) and saline control, which were administered at weeks 0, 2, and 6. The primary outcome measure for the present secondary analysis was change in the Snaith-Hamilton Pleasure Scale (SHAPS) total score between placebo- and infliximab-treated subjects from baseline to weeks 6 and 12. Plasma concentrations of TNF-α and soluble TNF receptors (sTNFR) 1 and 2 were assessed at weeks 0, 2, 6, and 12. Sixty eligible adults received treatment with infliximab (n=29) or placebo (n=31); 47 subjects completed the study (infliximab: n=21, placebo: n=26). Overall, infliximab-randomized subjects exhibited significantly larger increases in SHAPS total score, denoting greater reductions in anhedonic symptoms, when compared to placebo-randomized subjects (treatment × time interaction effect: χ2=7.15,df=2,p=0.03). Anti-anhedonic efficacy was moderated by baseline plasma levels of TNF-α and sTNFR1, but not by changes in TNF-α or sTNFR1 concentrations. Baseline and changes in sTNFR2 concentrations did not moderate anti-anhedonic efficacy. Infliximab significantly improved a measure of anhedonia relative to placebo in adults with bipolar I/II depression at week 6; intervention efficacy was not sustained 6 weeks after the final infusion.

Value of sTNF-R1 and linc0597 as indicators for disease activity and diagnosis of lupus nephritis.

To explore whether Soluble tumor necrosis factor-receptor 1 (sTNF-R1) and linc0597 can be used as indicators for disease activity and diagnosis of lupus nephritis (LN). Eighty LN patients treated in our hospital were enrolled as the LN group, while 60 Systemic Lupus Erythematosus (SLE) patients without nephritis were included in the SLE group, and 50 healthy subjects who conducted physical examination during the same period as the control group. After admission, 5 mL of venous blood was taken from all the study subjects to measure sTNF-R1 level and linc0597 expression by enzyme-linked immunosorbent assay (ELISA) and RT-qPCR respectively. In addition, the receiver operating characteristic (ROC) curves were employed to evaluate the diagnostic value of serum sTNF-R1 and linc0597 for LN, and Spearman correlation coefficient was adopted for the correlation between sTNF-R1, linc0597, and LN clinical disease Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). Moreover, the logistic multiple regression analysis was applied to analyze the independent risk factors affecting the complication of LN in SLE patients. The LN group presented significantly higher serum sTNF-R1 and linc0597 levels than the control group and the SLE group. Besides, ROC curve analysis revealed that sTNF-R1 and linc0597 had good clinical diagnostic value in LN and SLE. Furthermore, Spearman correlation coefficient indicated that serum sTNF-R1 and linc0597 were positively correlated with disease activity index SLEDAI (r=0.551, p<0.001; R =0.604, p<0.001). Moreover, multivariate Logistic regression analysis demonstrated that age (p=0.001), fever (p=0.004), arthralgia (p=0.034), serum uric acid (p=0.019), decreased complement C3 (p=0.023), ANA peripheral type (p=0.007), anti-ds-DNA antibody (p=0.003), ANCA (p=0.002), sTNF-R1 (p=0.001), and linc0597 (p<0.001) were all independent risk factors affecting the complication of LN in SLE patients. STNF-R1 and linc0597 can be used as the indicators for disease activity and diagnosis of LN.

Plasma levels of soluble TNF receptors are associated with cardiac function in patients with Chagas heart disease

BackgroundThe soluble receptors tumor necrosis factor-alpha (sTNFRs) can lead to an increase in the expression of tumor necrosis factor, increasing its detrimental to systemic inflammatory activation in Chagas cardiomyopathy (ChC). However, the correlation between sTNFRs levels, echocardiographic, and functional levels in patients with ChC remains unknown. This study aimed to verify the correlation between the plasma sTNFRs levels, echocardiographic, and NYHA functional levels in patients with ChC. MethodsSixty-four patients with ChD (54 ± 2 years, 44% males, NYHA I-II) were evaluated by anamnesis protocol, echocardiography, and plasma sTNFR1 and sTNFR2 measurement. Linear regression analysis and Student's t-test were used as appropriate. ResultsHigher plasma sTNFR1 and sTNFR2 levels were associate with worse systolic function (R2 = 0.10; p = 0.008 and R2 = 0.44; p < 0.001) and cardiac dilation (R2 = 0.13; p = 0.002 and R2 = 0.43; p < 0.001). Patients with systolic dysfunction and cardiac dilatation had higher sTNFRs levels (p < 0.001). There were no significant differences among NYHA functional classes for both sTNFRs. ConclusionPlasma sTNFR1 and sTNFR2 levels are associated with greater cardiac dilation and poor systolic function in ChC patients.

Effects of maltreatment on cortisol and inflammatory analytes

Adverse childhood experiences (ACEs) such as maltreatment have been associated with a disease risk phenotype that is characterized by altered regulation of the hypothalamic‐pituitary‐axis (HPA) and elevated pro‐inflammatory cytokines. However, there is evidence that different subtypes of ACEs elicit different physiological profiles. More specifically children with a history of physical abuse have lower cortisol levels whereas children with a history of sexual abuse have elevated cortisol levels compared to those in other maltreatment and non‐abused subgroups. The objective of the present study was to investigate if different maltreatment exposures, specifically physical and sexual abuse, are associated with HPA axis and inflammation by measuring levels of cortisol and inflammatory analytes. This study examines 156 young adults using the pilot data from the Niagara Longitudinal Heart Study (NLHS). Inflammatory analytes were assessed with blood serum. Retrospective chronic cortisol was measured through hair taken from the back of the scalp. Maltreatment was self‐reported using the Childhood Trust Event survey questionnaire. The NLHS study was approved by the Brock University’s Research Ethic Board. All analysis of variance models were not statistically significant. Those who reported sexual abuse had the highest cortisol levels. Those who reported physical abuse had the lowest cortisol levels compared to other subtypes. Interleukin 6 (IL6), C‐reactive protein (CRP), tumor necrosis factor α (TNFα), soluble tumor necrosis factor receptor 1 and 2 (sTNFR1 and sTNFR2) levels were higher among those with physical and sexual exposure compared to other subtypes. Levels of interleukin 6 receptor α (IL6Rα), glycoprotein (gp130), and interferon γ (IFNγ) were similar across all subtypes. The direction of cortisol levels pertaining to the subtypes of ACEs in the present study was consistent with the literature where physical abuse was linked to lower cortisol levels and sexual abuse was related to higher cortisol levels. Both physical and sexual abuse were trending towards statistical significance to some inflammatory analytes but not others. As the current pilot sample is underpowered for the effect sizes of cortisol and inflammatory analytes, the models used in analysis are likely to achieve statistical significance in a larger sample.Support or Funding InformationThe NLHS is funded by the Canadian Institutes of Health Research (CIHR #s 363774, 399332). ARRM is supported by the Ontario Graduate Scholarship (OGS) program.

Proteomic profiling of HTLV-1 carriers and ATL patients reveals sTNFR2 as a novel diagnostic biomarker for acute ATL

AbstractAdult T-cell leukemia/lymphoma (ATL) is a human T-cell leukemia virus type 1 (HTLV-1)–associated T-cell malignancy with generally poor prognosis. Although only ∼5% of HTLV-1 carriers progress to ATL, early diagnosis is challenging because of the lack of ATL biomarkers. In this study, we analyzed blood plasma profiles of asymptomatic HTLV-1 carriers (ACs); untreated ATL patients, including acute, lymphoma, smoldering, and chronic types; and ATL patients in remission. Through SOMAscan, expression levels of 1305 plasma proteins were analyzed in 85 samples (AC, n = 40; ATL, n = 40; remission, n = 5). Using gene set enrichment analysis and gene ontology, overrepresented pathways in ATL vs AC included angiogenesis, inflammation by cytokines and chemokines, interleukin-6 (IL-6)/JAK/STAT3, and notch signaling. In selecting candidate biomarkers, we focused on soluble tumor necrosis factor 2 (sTNFR2) because of its active role in enriched pathways, extreme significance (Welch's t test P < .00001), high discrimination capacity (area under the curve >0.90), and novelty in ATL research. Quantification of sTNFR2 in 102 plasma samples (AC, n = 30; ATL, n = 68; remission, n = 4) using enzyme-linked immunosorbent assay showed remarkable elevations in acute ATL, at least 10 times those of AC samples, and return of sTNFR2 to AC state levels after achieving remission. Flow cytometry and immunostaining validated the expression of TNFR2 in ATL cells. No correlation between sIL-2 and sTNFR2 levels in acute ATL was found, suggesting the possibility of sTNFR2 as an independent biomarker. Our findings represent the first extensive blood-based proteomic analysis of ATL, suggesting the potential clinical utility of sTNFR2 in diagnosing acute ATL.

Biomarkers of Inflammation in Heart Failure Patients with Reduced and Preserved Ejection Fractions: Multi-Ethnic Study of Atherosclerosis

Background: Limited evidence exists examining the relationship between biomarkers of inflammation and heart failure with reduced ejection fraction (HFrEF) or preserved ejection fraction (HFpEF) subtypes. Purpose: Examine the relationships between biomarkers of inflammation and incident heart failure subtypes in a diverse, population-based sample. Methods: Study sample included 6,814 adult (45-84 years of age) participants in the Multi-Ethnic Study of Atherosclerosis who were free of cardiovascular disease at baseline. The upper quartile of log-transformed C-reactive protein (CRP), interleukin-6 (IL-6), and soluble tumor necrosis factor-α receptor-1 (sTNFR1) was considered elevated. Heart failure participants with an ejection fraction (EF) <50% were considered HFrEF and those with a borderline EF (41-49%) or EF ≥50% were considered HFpEF. Results: During an average of 11.2 years of follow-up, there were 178 incident heart failure diagnoses; 57 with HFpEF, 86 with HFrEF, and 35 with unknown EF. Following adjustment for age, gender, race/ethnicity, blood pressure, waist circumference, smoking, LDL-C, triglycerides, HDL-C, atrial fibrillation, medications, and level of physical activity, logistic regression revealed significantly increased odds of HFrEF in those with elevated CRP (Odds Ratio [OR] 1.96; 95% Confidence Interval [CI] 1.18-3.13, p<0.01), sTNFR1 (OR 1.95; 95% CI 1.01-3.76, p=0.05) and IL-6 (OR 2.20; 95% CI 1.27-3.81, p<0.01). Comparatively, significantly increased odds of HFpEF were observed only in those with elevated IL-6 (OR 2.21; 95% CI 1.12-4.35, p<0.05). Conclusion: In a diverse sample of U.S. adults, elevated CRP, sTNFR1, and IL-6 levels were associated with increased odds of HFrEF and elevated IL-6 was significantly associated with HFpEF.

The Correlations Between TNF System and Memories in Chronic Insomnia Disorder

Objectives: To explore the changes of serum levels of tumor necrosis factors (TNF-α and TNF-β) and their soluble receptors (sTNF-R1 and sTNF-R2), and analyze their relationship between sleep quality and memory in the patients with chronic insomnia disorder (CID).Methods: Forty-four CID patients and 39 normal controls were enrolled in this study. Pittsburgh Sleep Quality Index (PSQI) and Nine-Box Maze Test (9BMT) were used to assess the sleep quality and memory function, respectively. The serum levels of TNF-α, TNF-β, sTNF-R1 and sTNF-R2 were examined by protein-chip.Results: Compared to the controls, the CID patients had significantly higher error numbers of the spatial working and object recognition memories (Ps < 0.05) in the 9BMT, with higher serum levels of TNF-α and TNF-β (Ps < 0.001), and lower levels of sTNF-R1 and sTNF-R2 (Ps < 0.001). The partial correlation analysis showed that the serum TNF-α and TNF-β positively but sTNF-R1 and sTNF-R2 negatively correlated with PSQI scores (Ps < 0.001). In the CID patients, the TNF-α positively correlated with the errors in the spatial working and object recognition memories (Ps < 0.05), whereas the TNF-β only positively correlated with the errors in the spatial working memory (P < 0.05).Conclusions: The CID patients had increased TNF-α and TNF-β and decreased sTNF-R1 and sTNF-R2 in peripheral blood, with the former being linked to specific memory impairments.

A comparison study of metabolic profiles, immunity, and brain gray matter volumes between patients with bipolar disorder and depressive disorder

BackgroundPrevious individual studies have shown the differences in inflammatory cytokines and gray matter volumes between bipolar disorder (BD) and unipolar depression (UD). However, few studies have investigated the association between pro-inflammatory cytokines and differences in brain gray matter volumes between BD and UD.MethodsIn this study, 72 BD patients and 64 UD patients were enrolled, with comparable gender and age distributions (33.8% males and an average age of 39.3 ± 13.7 years). Each participant underwent metabolic profiling (including body mass index (BMI), glucose, triglyceride, high-density lipoprotein (HDL), leptin, insulin, adiponectin), pro-inflammatory cytokine (including soluble interleukin-6 receptor (sIL-6R), soluble interleukin-2 receptor (sIL-2R), C-reactive protein (CRP), soluble tumor necrosis factor receptor type 1 (sTNF-R1) examinations, and structural magnetic resonance imaging exams. Voxel-based morphometry was performed to investigate the gray matter volume differences between BD and UD patients. Correlations between pro-inflammatory cytokines and the gray matter volume difference were analyzed.ResultsCompared to UD patients, the BD group had significantly higher BMI, and higher levels of sIL-6R and sTNF-R1 than the UD patients. The BMI significantly correlated with the level of pro-inflammatory cytokines. Adjusted for age, sex, BMI, duration of illness and total intracranial volume, the BD individuals had significantly more reduced gray matter volumes over 12 areas: R. cerebellar lobule VIII, R. putamen, L. putamen, R. superior frontal gyrus, L. lingual gyrus, L. precentral gyrus, R. fusiform gyrus, L. calcarine, R. precuneus, L. inferior temporal gyrus, L. hippocampus, and L. superior frontal gyrus. These 12 gray matter volume differences between BP and UD patients negatively correlated with sIL-6R and sTNF-R1 levels.ConclusionsOur results suggested that BD patients had higher BMI and pro-inflammatory cytokine levels in comparison to UD patients, especially IL-6 and sTNF-R1, which may contribute to greater gray matter reductions in BD patients in comparison to UD patients. The results support the neuro-inflammation pathophysiology mechanism in mood disorder. It is clinically important to monitor BMI, which, in this investigation, positively correlated with levels of inflammatory cytokines.

Functional Capacity and Inflammatory Mediators in Elderly Residents of Counties with Different Human Development Index.

A number of studies have indicated that certain factors, including socioeconomic status and education, are associated with the functional health status of the elderly. Another relevant factor in aging is chronic subliminal inflammation, with increased levels of circulating inflammatory cytokines such as interleukin-6 (IL-6), tumor necrosis factor α (TNF-α), and soluble tumor necrosis factor receptor 1 (sTNFR-1), commonly seen in the elderly. High levels of these inflammatory mediators could impair the functional capacity. In this respect, the aim of this cross-sectional study was to compare plasma levels of inflammatory mediators and functional capacity of older women living in three Brazilian counties with different Human Development Index. We evaluated 154 women aged ≥65 years, regardless of race and/or social status. IL-6 and sTNFR-1 plasma levels were measured by ELISA and the functional capacity by the Short Physical Performance Battery (SPPB) test. Comparison among groups was performed using one-way ANOVA with Bonferroni post hoc correction, Kruskal–Wallis, and Mann–Whitney U tests. Women that lived in one of the counties with high HDI had lower functional capacity (p < 0.001). The population from the county with the highest HDI had lower plasma levels of sTNFR-1 (p < 0.05). There was no significant difference in plasma levels of IL-6 (p > 0.05). Besides this, women from the counties with lower HDI had a higher number of self-reported diseases and higher income (p < 0.05). Women that lived in the county with the highest HDI had a higher average education level (p < 0.05). The results showed differences in functional capacity and plasma levels of sTNFR-1 between the counties. In addition, the level of education, family income, and number of self-reported diseases show regional diversities in the aging process, suggesting these factors having an influence on inflammatory mediators and functional capacity.