Higher Levels Of sTNFR1 Research Articles

Soluble tumor necrosis factor receptor type 1 predicts cardiorenal outcomes and better associated with distinct cardiovascular or renal outcomes than precedential renal or cardiovascular events in type 2 diabetes mellitus

Background: Inflammations are the crucial pathogenesis of chronic complications of type 2 diabetes mellitus (T2DM). Objectives: The timeline of cardiovascular and renal complications of T2DM and whether soluble tumor necrosis factor receptor type 1 (sTNFR1) levels predict cardiorenal outcomes were still elusive. Design: Prospectively observational study. Methods: Chinese patients with T2DM were enrolled. Cardiorenal composite events defined by either cardiovascular composite events (all-cause mortality, acute coronary syndrome, or non-fatal stroke) or renal composite events (a decline of >30% of renal function or worsening status of albuminuria) were followed. Associations of sTNFR1 levels and cardiovascular, renal, and cardiorenal composite events were analyzed in regression models presented by hazard ratio (HR) and 95% confidence interval (95% CI). Results: Among 370 subjects, 42 cardiovascular and 86 renal composite events occurred. Higher sTNFR1 levels were related to higher frequency and risks of cardiovascular composite events (HR 1.07, 95% CI 1.01–1.13, p = 0.009) and renal composite events (HR 1.05, 95% CI 1.02–1.09, p < 0.001). Occurrences of cardiovascular composite events were not predicted by precedential renal composite events. sTNFR1 levels were proved to be associated with risks of cardiorenal composite events in Cox regression sequential models (adjusted HR 1.04, 95% CI 1.00–1.08, p = 0.03). The results were consistent in all subgroup analyses. Conclusion: Levels of sTNFR1 were associated with cardiorenal complications of T2DM and the predictabilities of TNFR1 levels were better than precedential cardiovascular or renal events.

Levels of TNF-α and Soluble TNF Receptors in Normal-Weight, Overweight and Obese Patients with Dilated Non-Ischemic Cardiomyopathy: Does Anti-TNF Therapy Still Have Potential to Be Used in Heart Failure Depending on BMI?

We sought to measure the levels of adipokines, TNF-α and soluble receptors (sTNFr1, sTNFr2) in heart failure patients with reduced ejection fraction (HFrEF) due to non-ischemic cardiomyopathy (nDCM). A total of 123 patients with HFrEF due to nDCM were divided into three groups according to BMI: 34 (27.6%) normal weight, 56 (45.5%) overweight and 33 (26.8%) obese. A six-minute walk test, echocardiography and right heart catheterization were performed. Serum concentrations of adiponectin, leptin, NT-proBNP, blood hemoglobin, sodium, creatinine, ALAT, AspAT, bilirubin, CRP, lipids, TNF-α, sTNFr1 and sTNFr2 receptors were measured. Obese patients had the lowest NT-proBNP concentrations, significantly higher leptin levels and higher leptin/adiponectin ratios. The concentration of sTNFr1 was higher in normal-weight patients. In all groups, TNF-α concentrations correlated positively with sTNFr1 (p < 0.001). Higher levels of sTNFr1 were associated with higher sTNFr2 (p < 0.001) and CRP (p < 0.001). Moreover, the concentration of sTNFr2 positively correlated with CRP (p < 0.05) and adiponectin (p < 0.001). Levels of TNF-α were not associated with elevated CRP. This study demonstrated that changes in the concentrations of TNF and its receptors differ between groups of patients with different BMI. These findings suggest that the effective use of anti-TNF therapy is dependent not only on BMI, but also on concentrations of TNF-α receptors and other laboratory parameters.

Lithium exposure and chronic inflammation with activated macrophages and monocytes associated with atherosclerosis in bipolar disorder

BackgroundAtherosclerosis accounts for cardiovascular diseases (CVDs). This study aimed to explore the association between carotid intima-media thickness (CIMT), psycho-pharmacotherapy, and inflammatory markers along with other molecules related to atherosclerosis in bipolar disorder (BD). MethodsThe euthymic patients with bipolar I disorder (BD-I) aged over 20 years were recruited to measure CIMT through ultrasound and the blood levels of lipid profiles, soluble tumor necrosis factor receptor-1 (sTNF-R1), soluble interleukin-6 receptor (sIL-6R), monocyte chemoattractant protein-1, chitinase 3-like 1, endothelial adhesive proteins, and thrombin-antithrombin complex. ResultsParticipants were 103 BD-I patients with mean 44.3 years old. The ratio of lithium exposure in relation to illness chronicity and the current daily dosage of lithium therapy exhibited an inverse relationship with CIMT in the entire sample. After controlling for age and BMI, multivariate regression indicated that a higher lithium level was significantly associated with decreased CIMT in the entire sample, high-risk (those with CVDs or endocrine diseases, N = 48), middle-risk (those without CVDs and endocrine diseases, N = 55), and low-risk (those aged <45 years in the middle-risk subgroup, N = 43) subgroups. Furthermore, higher levels of sTNF-R1 in the entire sample and high-risk subgroup and sIL-6R in the middle- and low-risk subgroups were statistically associated with greater CIMT. LimitationThe age range was too wide to control for the effect of age on CIMT and medication. ConclusionsLithium exposure may be a protective factor for atherosclerosis progression in BD-I. The chronic inflammation in BD-I with activated macrophages and monocytes may link with the atherosclerosis development over time.

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.

Tumor necrosis factor receptor in Egyptian patients with bipolar disorder during mania: a case–controlled study

Background The role of inflammation has received increasing attention as a potential pathophysiological mechanism in bipolar disorder (BD). Objective To compare the level of soluble tumor necrosis factor-α receptor 1 (sTNFR1) in manic state of BD with healthy controls and investigate the relation between its level and the severity of BD. Patients and methods Serum levels of sTNFR1 were measured with enzyme-linked immunosorbent assay techniques in 44 patients with BD-I during the manic episode and 88 healthy controls recruited from Kasr Al Ainy Hospital, Cairo University. The severity of the manic symptoms was assessed using Young Mania Rating Scale. Results The level of sTNFR1 was higher in patients with BD-I, with the most recent episode manic, than in healthy control. Patients with BD-I, with the most recent episode manic, with psychotic features had higher levels of sTNFR1 than those without psychotic features. sTNFR1 level correlated with Young Mania Rating Scale scores. Conclusion High level of sTNFR1 may be considered as state marker in manic episodes in patients with BD-I. The more severe the disease, the higher the level of sTNFR1.

Adipokines, tumor necrosis factor and its receptors in female patients with systemic lupus erythematosus.

To analyze the association of adipokines and tumor necrosis factor α (TNFα) and its receptors with characteristics of systemic lupus erythematosus (SLE) and to investigate the correlation between adipokines and the TNF system. One hundred and thirty-six SLE women, aged ≥18 years old, were assessed. TNFα, soluble TNFα receptors 1 (sTNFR1) and 2 (sTNFR2) and adipokines were analyzed by ELISA kits. The median (IQR) of age was 41.5 (33.0-49.7) years old and of disease duration 11.3 (7.8-15.8) years. The median (IQR) of disease activity was 0 (0-4) and of damage index was 2 (1-3). Higher levels of sTNFR1 and sTNFR2 were associated with nephritis (p < 0.001 for both), and sTNFR1 (p = 0.025) and TNFα (p = 0.014) were positively associated with arthritis. Higher sTNFR1 levels were found in participants that were not using antimalarial drugs (p = 0.04). Independent correlation was found between sTNFR1 (β = 0.253; p = 0.003) and sTNFR2 (β = 0.297; p < 0.001) levels and disease activity and damage index (sTNFR1: β = 0.367; p < 0.001; sTNFR2: β = 0.335; p < 0.001). Higher adiponectin levels were independently associated with nephritis (p = 0.009) and antimalarial drugs use (p = 0.015). There was a positive correlation between leptin and sTNFR2 levels (p = 0.002) and between resistin levels and sTNFR1 (p < 0.001) and sTNFR2 (p < 0.001). The correlation between adipokines and TNF system allows a better understanding of the role of adipokines in the inflammatory response in SLE patients.

A Follow-Up Study of 50 Chronic Hepatitis C Patients: Adiponectin as a Resilience Biomarker for Major Depression

Objective: Major depression (MD) is a condition associated with both hepatitis C virus (HCV) infection and pegylated interferon (IFN)-α treatment. IFN induces a depressive syndrome that is associated with an inflammatory profile. We aimed to investigate whether there is any specific alteration in plasma biomarkers associated with MD. Methods: HCV-monoinfected patients, with and without IFN treatment, were followed up for 18 months and went through structured psychiatric evaluation. We assessed plasma levels of brain-derived neurotrophic factor, tumor necrosis factor (TNF) and its soluble type 1 and type 2 receptors (sTNFR1 and sTNFR2, respectively), and adipokines (adiponectin, leptin and resistin) using ELISA. Results: Among the 50 patients included in the study, 14 were treated with IFN during the follow-up. Being older, not married, presenting higher body mass index, higher liver inflammatory activity, lower baseline adiponectin levels and use of IFN were associated with MD development. Higher levels of sTNFR1 during IFN treatment were associated with sustained virological response. The lack of a control group without HCV infection did not allow any assumption of a biomarker change exclusively due to the infection itself. Conclusion: Adiponectin may be a resilience biomarker for MD in HCV-infected patients.

Inflammatory evidence for the psychosis continuum model

BackgroundInflammation and immune activation have been implicated in the pathophysiology of severe mental disorders. Previous studies of inflammatory markers, however, have been limited with somewhat inconsistent results. AimsWe aimed to determine the effect sizes of inflammatory marker alterations across diagnostic groups of the psychosis continuum and investigate association to antipsychotic medications. MethodsPlasma levels of soluble tumor necrosis factor receptor 1 (sTNF-R1), interleukin 1 receptor antagonist (IL-1Ra), osteoprotegerin (OPG), and von Willebrand factor (vWf) were measured in patients (n=992) with schizophrenia spectrum (SCZ, n=584), schizoaffective disorder (SA, n=93), affective spectrum disorders (AFF, n=315), and healthy controls (HC, n=638). ResultsLevels of sTNF-R1 (p=1.8×10−8, d=0.23) and IL-1Ra (p=0.002, d=0.16) were increased in patients compared to HC. The SCZ group had higher levels of sTNF-R1 (p=8.5×10−8, d=0.27) and IL-1Ra (p=5.9×10−5, d=0.25) compared to HC, and for sTNF-R1 this was also seen in the SA group (p=0.01, d=0.3) and in the AFF group (p=0.002, d=0.12). Further, IL-1Ra (p=0.004, d=0.25) and vWf (p=0.02, d=0.21) were increased in the SCZ compared to the AFF group. There was no significant association between inflammatory markers and use of antipsychotic medication. ConclusionWe demonstrate a small increase in sTNF-R1 and IL-1Ra in patients with severe mental disorders supporting a role of inflammatory mechanisms in disease pathophysiology. The increase was more pronounced in SCZ compared to AFF supporting a continuum psychosis model related to immune factors.

Soluble endoglin, transforming growth factor-Beta 1 and soluble tumor necrosis factor alpha receptors in different clinical manifestations of preeclampsia.

BackgroundDespite intensive research, the etiopathogenesis of preeclampsia (PE) remains uncertain. Inflammatory and angiogenic factors are thought to play considerable roles in this disease. The objective of this study was to investigate the association between soluble endoglin (sEng), transforming growth factor beta-1 (TGF-β1) and tumor necrosis factor alpha soluble receptors (sTNF-Rs) and the clinical manifestations of PE.MethodsPlasma levels of sEng, TGF-β1 and sTNF-Rs were determined by ELISA in 23 non-pregnant, 21 normotensive pregnant and 43 PE women. PE women were stratified into subgroups according to the severity [mild (n = 12) and severe (n = 31)] and onset-time of the disease [early (n = 19) and late (n = 24)].ResultsPregnancy was associated with higher levels of sEng, sTNF-R1 and sTNF-R2 than the non-pregnant state. Moreover, PE women had higher levels of sEng and sTNF-R1 than normotensive pregnant women. No difference was found in TGF-β1 levels, comparing the three study groups. Late PE had higher levels of sTNF-R1 and sTNF-R2 than early PE. No significant differences were found in sEng and TGF-β1 comparing early and late PE. sEng levels were higher in severe PE than in mild PE and no difference was found for TGF-β1, sTNF-R1 and sTNF-R2 levels. There was a positive correlation among sEng, TNF-R1 and sTNF-2 levels. Logistic regression analysis revealed that primiparity and sEng levels are independently associated with the development of PE. Furthermore, sEng levels are independently associated with the disease severity.ConclusionsThese results suggest that pregnancy is a condition associated with higher levels of anti-angiogenic and pro-inflammatory factors than the non-pregnant state and that PE is associated with an imbalance of these factors in the maternal circulation.

Soluble TNFα-receptor 1 as a predictor of coronary calcifications in patients after long-term cure of Cushing's syndrome.

Increased cardiovascular (CV) risk persists in Cushing's syndrome (CS), despite remission of hypercortisolism. The aim of this study was to evaluate prevalence of coronary artery disease in CS patients and its correlation with classical CV risk factors and inflammatory markers. Cardiac multidetector computed tomography (MDCT) was performed in 41 patients (7 men, 31 of pituitary origin, 29 cured, mean age: 48.6 ± 13 years), using 64-slice Toshiba Aquilion systems. Coronary atherosclerotic plaques were detected and coronary calcifications quantified by the Agatston score (AS). Clinical and biochemical parameters were correlated with the AS to identify possible surrogate markers of coronary disease. Normal values for clinical and biochemical parameters were obtained from a gender- and age-matched normal reference population (n = 82). CS patients with calcifications (AS > 0) (N = 13, 32%) had higher levels of sTNF-R1, homocysteine, triglycerides, blood pressure and body mass index than patients without calcifications (AS = 0) and those of normal reference population. Both groups of CS patients (AS > 0 and AS = 0) had elevated trunk fat mass and IL-6 compared to reference values. Patients with AS > 0 had less adiponectin and higher insulin, HOMA and fibrinogen than those found in normal reference population. sTNF-R1 correlated positively with AS and remained significant after adjusting for confounding factors. The same result was observed when we considered only cured CS patients. In our cohort of CS patients sTNF-R1 was a predictor of coronary calcifications. Since MDCT is an expensive technique not readily available in daily clinical practice, increased sTNF-R1 could be a marker of CV risk even in cured CS.

Inflammation and echocardiographic parameters of ventricular hypertrophy in a cohort with preserved cardiac function

ObjectiveTo investigate the association between inflammation and selective echocardiographic parameters (EP) characteristic for ventricular hypertrophy in cross-sectional and longitudinal population-based analyses.MethodsBaseline (711 men, 659 women: 45–83 years) and 4-year follow-up...

Inflammation marker and risk of pancreatic cancer: a nested case–control study within the EPIC cohort

Background:Established risk factors for pancreatic cancer include smoking, long-standing diabetes, high body fatness, and chronic pancreatitis, all of which can be characterised by aspects of inflammatory processes. However, prospective studies investigating the relation between inflammatory markers and pancreatic cancer risk are scarce.Methods:We conducted a nested case–control study within the European Prospective Investigation into Cancer and Nutrition, measuring prediagnostic blood levels of C-reactive protein (CRP), interleukin-6 (IL-6), and soluble receptors of tumour necrosis factor-α (sTNF-R1, R2) in 455 pancreatic cancer cases and 455 matched controls. Odds ratios (ORs) were estimated using conditional logistic regression models.Results:None of the inflammatory markers were significantly associated with risk of pancreatic cancer overall, although a borderline significant association was observed for higher circulating sTNF-R2 (crude OR=1.52 (95% confidence interval (CI) 0.97–2.39), highest vs lowest quartile). In women, however, higher sTNF-R1 levels were significantly associated with risk of pancreatic cancer (crude OR=1.97 (95% CI 1.02–3.79)). For sTNF-R2, risk associations seemed to be stronger for diabetic individuals and those with a higher BMI.Conclusion:Prospectively, CRP and IL-6 do not seem to have a role in our study with respect to risk of pancreatic cancer, whereas sTNF-R1 seemed to be a risk factor in women and sTNF-R2 might be a mediator in the risk relationship between overweight and diabetes with pancreatic cancer. Further large prospective studies are needed to clarify the role of proinflammatory proteins and cytokines in the pathogenesis of exocrine pancreatic cancer.

Increased plasma levels of soluble TNF receptor I in patients with bipolar disorder

Bipolar disorder (BD) has been associated with a proinflammatory state in which TNF-α seems to play a relevant role. The aim of the present study was to evaluate the plasma levels of TNF-α and its soluble receptors (sTNFR1 and sTNFR2) in BD patients in mania and euthymia in comparison with control subjects. We evaluated 53 BD patients (34 in mania and 19 in euthymia) and 38 healthy subjects. All subjects were assessed by the Mini-International Neuropsychiatry Interview (MINI-Plus). Patients were also evaluated by the Young Mania Rating Scale (YMRS) and by Hamilton Depression Rating Scale (HDRS). Plasma TNF-α and its soluble receptors were measured by ELISA. The plasma TNF-α and sTNFR2 levels did not differ between groups, but higher sTNFR1 levels were found in BD patients. Of note, BD patients in mania had higher sTNFR1 levels than BD patients in euthymia and controls. The sTNFR1 and sTNFR2 levels correlated with BD duration, and sTNFR2 levels correlated with age of patients. Our data indicate a proinflammatory status in BD patients during mania and further suggest that inflammatory mechanisms may be involved with the physiopathology of BD.

Increased serum levels of soluble tumor necrosis factor-α receptor-1 in patients with Parkinson's disease

Parkinson's disease (PD) is characterized by a progressive and irreversible loss of dopaminergic neurons. Inflammatory mechanisms have been implied in the pathophysiology of PD. In this study, we assessed serum levels of TNF-α and the soluble forms of their receptors, sTNFR1 and sTNFR2, in 46 PD patients and 23 control subjects. Patients with PD had higher levels of sTNFR1 ( p = 0.048). The concentration of sTNFR1 and sTNFR2 correlated with age ( p = 0.006 and p = 0.022, respectively). Higher levels of sTNFR1 were associated with later disease onset ( p = 0.048). These results corroborate the role of inflammatory events in the process of neurodegeneration in PD which can be of special relevance in the sporadic form of PD with later onset.

Persistent Body Fat Mass and Inflammatory Marker Increases after Long-Term Cure of Cushing’s Syndrome

Although increased central fat mass is characteristic of active Cushing's syndrome (CS), little is known about body composition and secretion of adipokines after long-term recovery of CS. The aim of this study was to evaluate central fat mass and its correlation with adipokines and cardiovascular risk factors in patients after long-term remission of CS. Thirty-seven women with CS in remission (27 of pituitary and 10 of adrenal origin; mean age, 50 +/- 14 yr; mean time of hormonal cure, 11 +/- 6 yr) were enrolled and compared to 14 women with active CS and 85 gender-, age-, and body mass index-matched healthy controls. Total and trunk fat mass were measured by dual-energy x-ray absorptiometry scanning. Laboratory parameters and adipokine levels [including adiponectin, visfatin, soluble TNFalpha-receptor 1 (sTNF-R1), sTNF-R2, and IL-6] were measured. Cured CS patients had more total and trunk fat mass than controls. Cured and active CS had higher levels of sTNF-R1 and IL-6 and lower adiponectin levels than controls. Higher insulin levels and blood pressure in both groups of CS patients and higher apolipoprotein B in cured CS were observed compared to controls. sTNF-R1 correlated positively with percentage of trunk fat mass and remained significant after adjusting for anthropometric parameters. Despite long-term cure, patients who have suffered CS exhibit persistent accumulation of central fat, as in active hypercortisolemia, with the consequent unfavorable adipokine profile, leading to a state of low-grade inflammation. This situation determines a persistent and increased cardiovascular risk in these patients.

Soluble TNF receptors are associated with Aβ metabolism and conversion to dementia in subjects with mild cognitive impairment

There is evidence supporting that tumor necrosis factor receptor (TNFR)-signaling can induce production of beta-amyloid (Aβ) in the brain. Moreover, amyloid-induced toxicity has been shown to be dependent on TNFR-signaling. However, it is still unclear whether TNFRs are involved in the early stages of dementia. We analyzed soluble TNFR1 and TNFR2 levels in plasma and cerebrospinal fluid (CSF) at baseline in 137 patients with mild cognitive impairment (MCI) and 30 age-matched controls. The MCI patients were followed for 4-6 years with an incidence of Alzheimer's disease (AD) or vascular dementia (VaD) of 15% per year. The patients with MCI who subsequently developed these forms of dementias had higher levels of sTNFR1 and sTNFR2 in both CSF and plasma already at baseline when compared to age-matched controls (p<0.05). In the CSF of MCI subjects and controls the levels of both sTNFR1 and sTNFR2 correlated strongly with β-site APP-cleaving enzyme 1 (BACE1) activity (r(s)=0.53-0.68, p<0.01) and Aβ 40 levels (r(s)=0.59-0.71, p<0.001). Similarly, both sTNFRs were associated with Aβ 40 (r(s)=0.39-0.46, p<0.05) in plasma. Finally, the levels of both sTNFRs correlated with the axonal damage marker tau in the CSF of MCI subjects and controls (r(s)=0.57-0.83, p<0.001). TNFR-signaling might be involved in the early pathogenesis of AD and VaD, and could be associated with beta-amyloid metabolism.

Usefulness of Type D Personality and Kidney Dysfunction as Predictors of Interpatient Variability in Inflammatory Activation in Chronic Heart Failure

Tumor necrosis factor-alpha (TNF-alpha), soluble TNF-alpha receptors 1 and 2 (sTNFR1/2), and interleukin (IL)-6 are powerful predictors of mortality in chronic heart failure (CHF). Little is known, however, about the origins of proinflammatory cytokine production or the determinants of substantial interpatient variability in inflammatory activation. We prospectively examined kidney dysfunction and Type D personality (tendency to experience and inhibit emotional distress) as predictors of interpatient variability in these markers of inflammatory activation. At baseline, 125 patients with CHF were assessed for kidney dysfunction and Type D. Serum levels of proinflammatory cytokines (TNF-alpha, sTNFR1, sTNFR2, IL-6), the anti-inflammatory cytokines IL-10, and IL-1 receptor antagonist were measured at 1-year follow-up. Type D patients had higher levels of sTNFR1 (p = 0.009) and sTNFR2 (p = 0.001) and lower levels of IL-10 (p = 0.006) than patients without Type D and kidney dysfunction. Patients with kidney dysfunction also had elevated levels of sTNFR1 and sTNFR2 (p <0.0001), but their IL-10 level was not decreased. Type D personality and kidney dysfunction predicted increased sTNFR1/IL-10 and sTNFR2/IL-10 ratios (p < or =0.007); Type D also predicted an increased IL-6/IL-10 ratio (p = 0.013). Other predictors were spironolactone and older age. After adjusting for these variables, the odds for elevated ratios (highest 20%) were still increased in Type D patients (all odd ratios >3.00). In conclusion, Type D personality and kidney dysfunction independently predicted unfavorable cytokine profiles in patients with CHF and may enhance our understanding of interpatient variability in inflammatory activation in these patients.

In Patients With Heart Failure Elevated Soluble TNF-Receptor 1 Is Associated With Higher Risk of Depression

Background Pro-inflammatory cytokines may contribute to the development and progression of heart failure (HF) and are also implicated in depressive disorders. In this cross-sectional study, we investigated whether systemic inflammation, as assessed by circulating levels of inflammatory cytokines, was associated with comorbid depression in patients with heart failure. Methods and Results Baseline clinical variables, depression status, and inflammatory marker levels were measured in 129 ambulatory HF patients. We hypothesized that pro-inflammatory cytokines, specifically tumor necrosis factor (TNF)-α, interleukin (IL)-1, and IL-6, would be elevated in HF patients with comorbid depression. In unadjusted analyses, levels of soluble TNF-α receptor1 (sTNFr1) were significantly higher among depressed (1.6 ng/mL), compared with nondepressed (1.1 ng/mL), HF patients ( P = .01). After multivariate adjustment, compared with patients in the lowest quartile of sTNFr1 levels, those in the highest quartile had an adjusted near 5-fold higher risk of depression (OR 4.6, 95% CI 1.2–17.3; P for trend .008). The subgroup of patients on antidepressants but not currently depressed had a trend toward higher levels of sTNFr1, suggesting that antidepressants may not lower cytokine levels even when adequately treating depressive symptoms. IL-1β and IL-6 levels were not significantly different among depressed versus nondepressed HF patients. Conclusions In this cross-sectional analysis, HF patients with comorbid depression, compared with nondepressed HF patients, had higher levels of sTNFr1 and trend toward higher levels of sTNFr1 even when adequately treated for depression.

Prognostic values of α 2-macroglobulin, fibrinogen and albumin in regards to mortality and frailty in old rats

The study aimed to determine if acute phase proteins (APP) are markers of frailty in old rats. We evaluated in male Wistar rats at 96 weeks of age ( n = 72) whether single measurements of α 2-macroglobulin, fibrinogen and albumin are predictive of mortality, body weight loss and inflammatory status during a 10-week follow-up period. Rats were clustered depending on levels of these APP at baseline. Rats with extremely high levels of α 2-macroglobulin or fibrinogen (upper quartiles), or extremely low level of albumin (lower quartile), had an 11.6, 8.1 and 5.3-fold higher risk of mortality, respectively, than other rats. Body weight loss was negatively correlated with α 2-macroglobulin, a trend was observed with fibrinogen ( P = 0.08) but not with albumin. Rats with fibrinogen levels >4.0 g/L or α 2-macroglobulin levels >91 mg/L (respective top halves) at 96 weeks of age had higher levels of α 2-macroglobulin and fibrinogen and lower levels of albumin throughout the follow-up period and higher levels of sTNFR-1 and lipopolysaccharide-binding protein at 106 weeks of age. Highest levels of α 2-macroglobulin, fibrinogen and lowest albumin were predictive of mortality, whereas moderate levels of α 2-macroglobulin and fibrinogen were, according to body weight loss and inflammatory status, markers of frailty in old rats.