Lower Interleukin-6 Concentrations Research Articles

Interleukin 6 Signalling in Heart Failure With Preserved and Reduced Ejection Fraction.

Identification of interleukin-6 (IL-6) signaling pathways in patients with chronic heart failure (CHF). The diversity of IL-6 effects is due to the presence of classical signaling and trans-signaling pathways. The study included 164 patients with CHF hospitalized for acute decompensated heart failure (ADHF), of which 129 had reduced left ventricular ejection fraction (HFrEF), and 35 had preserved ejection fraction (HFpEF). Blood concentrations of IL-6, soluble IL-6 receptor (sIL-6R), soluble transducer protein gp130 (sgp130), and high-sensitivity C-reactive protein (hsCRP) were measured. Patients with HFpEF had lower concentrations of IL-6 (6.15 [2.78, 10.65] pg/ml) and hsCRP (11.27 [5.84, 24.40] mg/ml) than patients with HFrEF (9.20 [4.70; 15.62] pg/ml and 17.23 [8.70; 34.51 mg/ml], respectively). In contrast, concentrations of rIL-6R were higher in HFpEF (59.06 [40.00; 75.85] ng/ml) than in HFrEF (49.15 [38.20; 64.89] ng/ml). Concentrations of sgp130 were not significantly different. In patients with HFrEF, positive correlations were found between the concentrations of IL-6 and hsCRP, IL-6 and rIL-6R, and IL-6 and sgp130, while in patients with HFpEF, there was a correlation only between IL-6 and hsCRP, which appeared stronger than in patients with HFrEF (r=0.698; p<0.001 and r=0.297; p<0.05, respectively). Classical IL-6 signaling and trans-signaling are expressed to different degrees in patients with HFrEF and HFpEF in ADHF. The results of the study supplement the existing knowledge about the pathogenesis of inflammation in CHF and may contribute to the development of new methods and approaches to the treatment of the disease.

Dietary Patterns, Nutritional Status and Inflammatory Biomarkers in Adolescents from the RPS Birth Cohort Consortium.

This study aimed to identify the dietary patterns (DPs) of adolescents and assess indicators of subclinical inflammation. It was a cross-sectional study aligned with the RPS cohort with data from São Luís, Maranhão, Brazil. We evaluated 511 adolescents between 18-19 years old. DPs were identified with a factor analysis of the principal components. Nutritional status was assessed with body mass index and body fat percentages. Hierarchical modeling was performed using a linear regression to estimate the beta coefficient (β) of the independent variables with the dependent variables interleukin-6 and high-sensitivity C-reactive protein (hs-CRP). Five DPs were identified: energy-dense, sugar-sweetened beverages and breakfast cereals, prudent, traditional Brazilian and alcoholic and energy beverages. Greater adherence to the prudent DP was associated with a lower concentration of interleukin-6 (β = -0.11; p value = 0.040). Greater adherence to the DP "traditional Brazilian" and "alcoholic and energy beverages" were associated with increased IL-6, mediated by the nutritional status. A higher BMI (β = 0.36; p value = <0.001) and %BF (β = 0.02; p value = 0.014) were associated with higher hs-CRP concentrations. The nutritional status and "prudent" pattern were associated with inflammatory biomarkers. These findings show that a higher consumption of fresh and minimally processed foods and the adequacy of the nutritional status are protective factors for the inflammatory process.

Individuals with depression exhibiting a pro-inflammatory phenotype receiving omega-3 polyunsaturated fatty acids experience improved motivation-related cognitive function: Preliminary results from a randomized controlled trial

Cognitive impairment related to major depressive disorder (MDD) is highly prevalent, debilitating and is lacking in effective treatments; dysregulated inflammatory physiology is a putative mechanism and may represent a therapeutic target. In depressed individuals exhibiting a pro-inflammatory phenotype who were enrolled in a 12-week randomized placebo-controlled trial of 3 doses of omega-3 polyunsaturated fatty acids (ω-3-FA), we examined: (i) the relationship between dysregulated inflammatory physiology and baseline cognitive impairment; (ii) improvement in cognitive impairment following treatment; and (iii) the association between baseline inflammatory biomarkers and change in cognitive impairment for those receiving treatment. We randomized 61 unmedicated adults aged 45.50 years (75% female) with DSM-5 MDD, body mass index >25 kg/m2, and C-reactive protein (CRP) ≥3.0 mg/L to three doses of ω-3-FA (1, 2, or 4 g daily) or matching placebo. Analyses focused on 45 study completers who had inflammatory biomarkers assessed [circulating CRP, interleukin-6 (IL-6) and tumor necrosis factor-α (TNFα) as well as lipopolysaccharide (LPS)-stimulated concentrations of IL-6 and TNFα in peripheral blood mononuclear cells (PBMC)] and on the highest dose ω-3-FA (4 g daily; n = 11) compared to placebo (n = 10). Impairment in motivational symptoms (e.g., alertness, energy, enthusiasm) and higher-order cognitive functions (e.g., word-finding, memory) were assessed by a validated self-report measure. Among all 45 participants at baseline, lower concentrations of IL-6 in LPS-stimulated PBMC were associated with greater impairment in higher-order cognitive functions (r = −0.35, p = .02). Based on hierarchical linear modeling, individuals receiving 4 g/day of ω-3-FA reported significant improvement in motivational symptoms compared to placebo (B = −0.07, p = .03); in the 4 g/day group, lower baseline concentrations of TNFα in LPS-stimulated PBMC were associated with significant improvement in motivational symptoms (Ρ = .71, p = .02) following treatment. In this exploratory clinical trial, daily supplementation with 4 g of ω-3-FA improves motivational symptoms in depressed individuals exhibiting an inflammatory phenotype.

Abstract 14039: The Cardioprotective and Anti-Inflammatory Effect of Inhaled Nitric Oxide During Fontan Surgery: A Prospective Randomized Study

Introduction: Open heart surgery that requires cardiopulmonary by-pass (CPB) evokes tremendous stress and inflammatory responses, affecting postoperative organ function, morbidity, and mortality. Although part of this reaction triggers protective and anti-inflammatory phenomena, it is harmful, particularly in patients with single ventricle congenital heart defects during Fontan surgery. Unfortunately, there is no perfect anti-inflammatory and stress defence strategy despite decades of research. Hypothesis: This study aimed to investigate the influence of nitric oxide (NO) inhaled directly into the oxygenator during CPB on a proteome profile of inflammatory cytokines, metabolic response markers, heart and lung protection indicators, and the early clinical outcomes. Methods: The study involved 115 patients randomized to the Fontan-NO group, receiving NO inhalation (n=48) and the Fontan group, not receiving NO (n=49). Eighteen patients were excluded from the study. The clinical data were prospectively analyzed. Proteome profiler essays were used for repeated measurements of investigated analytes. Results: Fontan-NO patients had significantly lower levels of lactate (p=0.04) and glucose (p=0.02), lower pulmonary artery pressure (p=0.03) and catecholamine index (p=0.042), shorter ventilatory support time (p=0.03) and ICU stay (p=0.04). Plasma factors analysis has shown a significantly higher concentration of interleukin-10, tissue inhibitor of metalloproteinase, prolactin, and angiopoietin and a lower concentration of interleukin-6, interleukin-8, interleukin-1β, granulocyte-macrophage colony-stimulating factor, pentraxin, matrix metalloproteinase-8, troponin-I, CK-MB, and insulin in Fontan-NO group. Multiple regression analysis revealed the influence of Il-6 and Il-8 on respiratory support time and ICU stay and the relationship between catecholamine index, duration of effusions, and indicators of myocardial damage. Conclusions: NO inhaled into the oxygenator during CPB can alleviate the inflammatory response, improve myocardial and lung protection, and reduce metabolic stress in patients with a single ventricle undergoing Fontan surgery. The observed effects can influence short-term clinical outcomes.

The cardioprotective and anti-inflammatory effect of inhaled nitric oxide during Fontan surgery in patients with single ventricle congenital heart defects: a prospective randomized study

BackgroundFontan surgery with cardiopulmonary bypass (CPB) causes tremendous systemic stress and inflammatory responses, affecting postoperative organ function, morbidity, and mortality. Although this reaction triggers partially protective anti-inflammatory responses, it is harmful in patients with single ventricle congenital heart defects. Despite decades of research, an effective anti-inflammatory and stress defense strategy is lacking. This study investigated the influence of inhaled nitric oxide (NO) during CPB on early clinical results, including the duration of postoperative respiratory support as a primary outcome and a panel of laboratory analytes.MethodsIn this study, 115 patients were randomized to the Fontan-NO group (n = 48) and the Fontan group (n = 49). Eighteen patients were excluded from the study. The Fontan-NO group received NO inhaled directly into the oxygenator during CPB. Clinical data were collected, and blood samples were drawn for analysis at repeated intervals. Multiplex assays were used to analyze a proteome profile of molecules involved in stress response, inflammation, metabolic reactions, as well as heart and lung protection.ResultsFontan-NO patients had significantly shorter respiratory support time with a median of 9.3 h (7.0; 13,2) vs 13.9 h (3.7; 18.5) by the absolute difference of 4.6 h [95% confidence interval, − 30.9 to 12.3; (p = 0.03)]. In addition, they have a shorter time in intensive care (p = 0.04) and lower pulmonary artery pressure after CPB discontinuation (p = 0.04), 4 h (p = 0.03) and 8 h (p = 0.03) after surgery. Fontan-NO patients also had a lower concentration of lactates (p = 0.04) and glucose after separation from CPB (p = 0.02) and lower catecholamine index (p = 0.042). Plasma factors analysis has shown a significantly higher concentration of interleukin-10, and a lower concentration of interleukin-6, interleukin-8, interleukin-1β, pentraxin, matrix metalloproteinase-8, troponin-I, creatine kinase myocardial band (CK-MB), and insulin in Fontan-NO group.ConclusionsNO inhaled into the oxygenator during CPB can improve short-term clinical outcomes. It shortens intubation time and intensive care time. It reduces inflammatory response, improves myocardial and lung protection, and diminishes metabolic stress in patients with a single ventricle undergoing Fontan surgery.Trial registration number: The trial was preregistered, supervised, and supported by The Polish National Science Center (NCN/01/B/NZ5/04246).

Abstract P084: Sex Differences In Testosterone On Interleukin-6 At Baseline And In Response To Mental Stress

Introduction: Young and middle-aged women with ischemic heart disease are a high-risk group for morbidity and mortality particularly after a myocardial infarction (MI). This group exhibits higher concentrations of the inflammatory cytokine interleukin-6 (IL-6) at baseline and in response to mental stress compared to men. The reasons for these differences are unknown; however, sex hormones may play a role. While testosterone has been shown to have anti-inflammatory effects among men; the role of testosterone on inflammatory cytokines among women has been understudied, and no research has examined the influence of testosterone on IL-6 response to stress. Hypothesis: Among young and middle-aged patients with a recent MI, higher concentrations of testosterone have anti-inflammatory effects among men at baseline and in response to mental stress; but are associated with greater inflammation among women. Methods: We studied 269 patients 61 years old or younger who were hospitalized for a MI in the previous 8 months. We measured plasma IL-6 (pg/mL) before and 90 minutes after mental stress (speech task). Inflammatory response was defined as the difference between IL-6 levels 90-minutes post mental stress and resting values. Serum free testosterone (pg/mL) was measured before mental stress. Differences across sex and time were examined with mixed models for repeated measures after natural log-transformation of IL-6. Results: The mean age was 51 years (range: 26-61); 48% were women and 64% African American. Mean values of free testosterone among men and women were 12.6 pg/mL (range: 0.9-29.0) and 1.8 pg/mL (range: 0.3-15.6), respectively. After adjusting for demographic factors (age, race, income), lifestyle and medical history (BMI, hypertension, diabetes, depression) and medication use, the association of testosterone with the IL-6 response to stress differed by sex (p for testosterone-by-sex-by-time interaction = 0.06). Among men, higher levels of testosterone were associated with lower concentrations of IL-6 at rest (β = -0.04; p = &lt;.0001), but was attenuated after stress (β = -0.001; p = 0.93). This change in slopes across time or inflammatory response for men was significant (p = &lt;.0001). In contrast, among women, higher levels of testosterone tended to be associated with higher IL-6 at rest (β = 0.04; p = 0.07) and after stress (β = 0.04; p = 0.14), indicating no change between time points or inflammatory response to stress (p=0.75). Conclusions: Among young and middle-aged survivors of a recent MI, higher concentrations of free testosterone are associated with lower inflammation among men, but with an opposite trend of higher inflammation among women.

Dietary 25(OH)D3 supplementation to gestating and lactating sows and their progeny affects growth performance, carcass characteristics, blood profiles and myogenic regulatory factor-related gene expression in wean-finish pigs.

ObjectiveThis experiment investigated the effects of supplementing vitamin D3-fortified sow and progeny diets with 25(OH)D3 on growth performance, carcass characteristics, immunity, and pork meat quality.MethodsThe present study involved the assessment of supplementing the diet of sows and their progeny with or without 25 (OH)D3 in a 2×2 factorial arrangement on the performance and production characteristics of wean-finish pigs. Forty-eight multiparous sows were assigned to a basal diet containing 2000 IU/kg vitamin D3 and supplemented without (CON) or with (TRT) 50 μg/kg 25 (OH)D3. At weaning, a total of 80 pigs each from CON and TRT sows were allocated to weaning and growing-finishing basal diets fortified with 2,500 and 1,750 IU/kg vitamin D3 respectively and supplemented without or with 50 μg/kg 25(OH)D3.ResultsSows fed 25(OH)D3-supplemented diets improved pre-weaning growth rate of nursing piglets. A significant sow and pig weaning diet effect was observed for growth rate and feed efficiency (p<0.05) during days 1 to 42 post-weaning. Pigs consuming 25(OH)D3-supplemented diets gained weight faster (p = 0.016), ate more (p = 0.044) and tended to convert feed to gain more efficiently (p = 0.088) than those fed CON diet between days 98 and 140 post-weaning. Supplemental 25(OH)D3 improved water holding capacity and reduced drip loss of pork meat, increased serum 25(OH)D3 level, produced higher interleukin-1 and lower interleukin-6 concentrations in blood circulation, downregulated myostatin (MSTN) and upregulated myogenic differentiation (MYOD) and myogenic factor 5 (MYF5) gene expressions (p<0.05).ConclusionSupplementing vitamin D3-fortified sow and wean-finish pig diets with 50 μg/kg 25(OH)D3 significantly improved production performance suggesting their current dietary vitamin D3 levels are insufficient. In fulfilling the total need for vitamin D, it is strongly recommended to add 50 μg/kg 25(OH)D3 “on top” to practical vitamin D3-fortified sow and wean-finish pig diets deployed under commercial conditions.

Depression symptoms mediate the association between workplace stress and interleukin 6 in women, but not men: The Whitehall II study

Workplace stress and depression are positively related with inflammation, and each other. Low-grade inflammation and concurrent high levels of workplace stress or depression has been related with future morbidity. The potential pathway between constructs however, remains elusive. For the first time, this study explored the concurrent relationship between workplace stress, depressive symptomology and low-grade inflammation, and considered the role of gender in these relationships. Data from the Whitehall II cohort study (N ​= ​2528, Mage ​= ​57.01, 23.7% females) provided measures of workplace stress (job demand-control; JDC), depressive symptomology (Centre for Epidemiological Studies Depression scale; CES-D) and circulating inflammatory markers, interleukin-6 (IL-6) and C-reactive protein (CRP) collected on the same day from a single time point. Females had higher workplace stress, depressive symptoms and lower serum IL-6 concentrations. For males, higher workplace stress was associated with higher depressive symptoms. For females, higher depressive symptoms were related with elevated IL-6 levels, and both higher workplace stress and IL-6 levels were associated with higher depressive symptoms. Higher depressive symptoms were related with higher CRP levels in men only. Higher depressive symptoms statistically mediated the relationship between higher workplace stress and IL-6 levels in females only, b ​= ​0.016, CI [0.002, 0.039]. Females in this large cohort had higher levels of job strain, depression and lower IL-6 concentrations than males. In females, higher depressive symptoms were associated with higher serum IL-6 levels and workplace stress was not. Considered together, these findings suggest that low job control may be more apparent in females than males, but it is primarily negative affect that drives the positive relationship between work stress and serum IL-6 concentrations in females. Replicating the current design with a suitably proximal follow-up is required to determine if the associations identified are causal.

Rapid and Selective Biomarker Detection with Conductometric Sensors.

The biomarker detection in human body fluids is crucial as biomarkers are important in diagnosing diseases. Conventional invasive techniques for biomarker detection are associated with infection, tissue damage, and discomfort. Non-invasive devices are an attractive alternative. Here, metal oxide (oxygen-deficient zinc oxide, ZnO) based conductometric sensors with two-terminal electrodes for rapid detection of biomarkers in real-time, are presented. This platform can be engineered for non-invasive, sensitive, and on-demand selective detection of biomarkers based on surface functionalization. The three novelties in this biosensing technique include an on-demand target selection device platform, short (<10min) incubation times, and real-time monitoring of the biomarker of interest by electrical (resistance change) measurements. Cardiac inflammatory biomarkers interleukin6 (IL-6) and C-reactive protein (CRP) are used as the model antigens. The devices can detect 100× lower concentration of IL-6 than healthy levels in human saliva and sweat and 1000× and ≈50× lower CRP concentrations than healthy levels in human saliva and sweat, respectively. The devices show high selectivity for IL-6 and CRP antigens when tested with a mixture of biomarkers. This sensor platform can be extended to selective measurements for viruses or DNA screening, which enables a new category of compact and rapid point-of-care medical devices.

Analyses of interleukin-6, presepsin and pentraxin-3 in the diagnosis and severity of late-onset preeclampsia

Introduction The etiology/pathophysiology of preeclampsia remains an enigma. Maternal inflammation (humoral and cellular) is a key factor in the etiology of late-onset preeclampsia (L-PrE). Presepsin is split out from the phagocytes membranes after phagocytosis. It is known as a novel inflammation marker. To our knowledge, this is the first study in literature in English to investigate maternal blood concentrations of presepsin in preeclampsia and healthy pregnant women. Methods We examined maternal plasma interleukin-6, presepsin and pentraxin-3 concentrations in pregnant women with (n = 44) and without L-PrE (n = 44). These three inflammatory markers concentrations measured using enzyme-linked immunosorbent assays were compared. Results The mean maternal age and gestational age at sampling are similar in the both groups (p ≥ .05). Interleukin-6, presepsin and pentraxin-3 concentrations differed between the groups (p < .05). There was no difference between the three inflammatory markers concentrations in patients with mild (22 patients) and severe (22 patients) preeclampsia in L-PrE (p ≥ .05). A significant discriminative role of interleukin-6, presepsin and pentraxin-3 for presence of L-PrE, with cutoff values of 39.74 pg/mL, 309.88 mg/L and 34.96 ng/mL, respectively, were reported in a ROC curve analysis. When the patients with and without small for gestational age infants (12 patients and 76 patients, respectively) were compared, it was determined that there was no differences between the interleukin-6, but there were differences between the presepsin and pentraxin-3 concentrations (p = .016, p = .008, respectively). Conclusion Lower concentrations of interleukin-6/presepsin and higher concentrations of pentraxin-3 were associated with the development of preeclampsia. Further investigations of inflammatory/immunity markers in pregnancy are required and may ultimately lead to novel therapeutic approaches to treat complications of pregnancy.

Dysbiosis of lower respiratory tract microbiome are associated with inflammation and microbial function variety

BackgroundLower respiratory tract (LRT) microbiome has been reported to associate with pulmonary diseases. Unregulated inflammation is an underlying cause of variable lung diseases. The lung microbiome may play an important role in the smoking-induced inflammatory lung diseases. What’s more, the function of microbiome may be more important for understanding how microbes interact with host. Our study aims to explore the effects of smoking on the lower respiratory tract microbiome, the association between variation of lower respiratory tract microbiome and inflammation and whether smoking exposure changes the function of lower respiratory tract microbime.MethodsForty male mice were randomly divided into smoking group and non-smoking group, and the smoking group was exposed to cigarette smoke for 2 h per day for 90 days. After experiment, the blood samples were collected to measure the concentration of interleukin-6 (IL-6) and C reactive protein (CRP) by ELISA. Lung tissue samples were used to detect the community and diversity of lower respiratory tract microbiome through 16S rRNA gene quantification and sequencing technology. ANOSIM and STAMP were performed to analyze the differences of the microbial community structure between smoking group and non-smoking group. SPSS 24.0 software was used to analyze the correlations between microbiome and inflammation mediators through scatter plots and Spearman correlation coefficient. Microbial metabolic function was predicted by PICRUSt based on the 16 s rRNA gene quantification and sequencing results. PATRIC database was searched for the potential pathogenic bacteria in lower respiratory tract.ResultsOur results suggested that smoking had markedly effects on the microbiota structure of lower respiratory tract based on Bray-Curtis distance (R2 = 0.084, p = 0.005) and on unweighted uniFrac distance (R2 = 0.131, p = 0.002). Smoking mainly affected the abundance of microbiome which belong to Proteobacteria phyla and Firmicutes phyla. Moreover, our results also found that smoking increased the abundance of Acinetobacter, Bacillus and Staphylococcus, which were defined as pathogenic bacteria. Inflammatory mediators were observed to associate with certain microbiome at every level. Most of microbiome which were associated with inflammation belonged to Proteobacteria phyla or Firmicutes phyla. Moreover, we found that the decreased microbiome in smoking group, including Oceanospirillales, Desulfuromonadales, Nesterenkonia, and Lactobacillaceae, all were negatively correlated with IL-6 or CRP. Based on the level of inflammation, the abundance of microbiome differs. At genus level, Lactobacillus, Pelagibacterium, Geobacter and Zoogloea were significantly higher in smoking group with lower IL-6 concentration. The abundance of microbiome was not observed any statistical difference in subgroups with different weight. Three dominant genus, defined as pathogen, were found higher in the smoking group. The microbial functional prediction analysis revealed that ABC-type transport systems, transcription factors, amino acide transport and metabolism, arginine and proline metabolism et al. were distinctively decreased in smoking group, while the proportions of replication, recombination and repair, ribosome, DNA repair and recombination proteins were increased in smoking group (q < 0.05).ConclusionsMembers of Proteobacteria phyla and Firmicutes phyla played an important role in the microbial community composition and keeping a relatively balanced homeostasis. Microbiome dysbiosis might break the balance of immune system to drive lung inflammation. There might exist potential probiotics in lower respiratory tract, such as Lactobacillaceae. The altered function of Lower respiratory tract microbiome under smoking exposure may affect the physiological homeostasis of host.

Effect of epidural labor analgesia with different concentrations of ropivacaine combined with sufentanil on fever

Objective To evaluate the effect of epidural labor analgesia with different concentrations of ropivacaine combined with sufentanil on fever. Methods A total of 104 healthy parturients, of American Society of Anesthesiologists physical status Ⅰ or Ⅱ, with New York Heart Association gradeⅠ or Ⅱ, with body height 150-175 cm, weighing 50-90 kg, at 37-45 weeks of gestation, scheduled for elective labor analgesia, were divided into 0.075% ropivacaine group (group R1, n=51) and 0.125% ropivacaine group (group R2, n=53) by a random number table method.Epidural labor analgesia was performed with 0.075% ropivacaine plus 0.25 μg/ml sufentanil and with 0.125% ropivacaine plus 0.25 μg/ml sufentanil in group R1 and group R2, respectively, to maintain visual analog scale score<3.Body temperature was measured before analgesia (T0), at 30 min, 1, 3 and 5 h of analgesia (T1-4), immediately after delivery and at 2 h after delivery (T5, 6). Venous blood samples were collected at T0, 3, 5 to detect the concentration of interleukin-6 (IL-6) in serum.The incidence of fever, plane of anesthesia, fluid infusion rate, consumption of sufentanil and ropivacaine, the number of increment of drugs and length of labor were recorded. Results Compared with group R1, the degree of increase in body temperature was significantly increased at T1-6, the consumption of ropivacaine and concentration of IL-6 at T3 were increased in group R2 (P 0.05). Conclusion Epidural labor analgesia with different concentrations of ropivacaine combined with sufentanil exerts no effect on fever, 0.075% ropivacaine induces less changes in body temperature of parturients than 0.125% ropivacaine, which is related to the lower concentration of IL-6. Key words: Piperidines; Sufentanil; Analgesia, epidural; Parturition; Fever

Socioeconomic status, psychological resources, and inflammatory markers: Results from the MIDUS study.

Our objective was to investigate interactions of psychological resources and socioeconomic status (SES)-as well as potential gender differences and the explanatory role of childhood and adult stress exposures, health behaviors, and negative and positive affect-in predicting markers of systemic inflammation. We utilized a sample of adults from the Midlife Development in the U.S. (MIDUS) study who provided biomarker data (N = 1,152). SES was operationalized as a composite of education, income, and occupational prestige, and the psychological resources construct was operationalized as a latent factor measured with optimism, perceived control, and self-esteem. Linear regression models examined these 2 factors and their interaction in predicting interleukin-6 (IL-6) and C-reactive protein (CRP) measured on average 2 years later, as well as 3-way interactions involving gender and the impact of covariate adjustment. Psychological resources interacted with SES in men (for IL-6: p < .001; for CRP: p = .04) but not in women. In men, greater psychological resources was associated with lower concentrations of IL-6 at lower levels of SES but higher concentrations of both markers at higher levels of SES. The inverse association between resources and IL-6 at low SES was moderately attenuated upon adjustment for negative affect. Socioeconomic status might modulate the linkage between psychological resources and systemic inflammation in men. At lower levels of SES, resources may be related to lower inflammation in part through lower negative affect. Associations with higher inflammation at higher SES add to growing evidence suggesting that adaptive psychological characteristics may be associated with markers of poorer physiological function under certain conditions. (PsycINFO Database Record

Differential secretion of adipokines from subcutaneous and visceral adipose tissue in healthy dogs: Association with body condition and response to troglitazone

This study aimed to determine the effects of body condition, fat depot, and a peroxisome proliferator-activated receptor γ-agonist (troglitazone) on secretion of adiponectin, interleukin-6 (IL6), and tumor necrosis factor-α (TNFα) from adipose tissue of healthy dogs. Subcutaneous and omental visceral adipose tissue samples were collected from 16 healthy intact female dogs, and body condition score (range 4–8/9) was determined. Concentrations of adiponectin were measured in mature adipocytes cultures and concentrations of IL6 and TNFα were measured in stromovascular cells cultures after 48 h incubation in fresh control medium, or fresh medium containing 10 µM troglitazone.Mature adipocytes and stromovascular cells of subcutaneous origin secreted higher concentrations of adiponectin and lower concentration of IL6 and TNFα, respectively, than corresponding cells of visceral origin, in both the control (P = 0.015, P = 0.004, and P = 0.016, respectively) and troglitazone-treated cultures (P < 0.001, P = 0.004, and P = 0.016, respectively). Troglitazone increased adiponectin secretion from mature adipocytes in visceral (P = 0.019), but not in subcutaneous fat cultures (P = 0.4). Troglitazone decreased IL6 and TNFα secretion from stromovascular cells both in visceral (P = 0.047 and P = 0.016, respectively) and subcutaneous (P = 0.047 and P = 0.016, respectively) fat cultures. Higher body condition score was associated with lower secretion of adiponectin from mature adipocytes (P = 0.007), lower secretion of IL6 (P = 0.040) and higher secretion of TNFα (P = 0.040) from stromovascular cells. This study showed differential secretion of adipokines by subcutaneous and visceral fat depots in dogs and association between body condition and adipokine secretion. Activation of PPARγ altered adipokine secretion.

Interleukin-6 and C-reactive protein, successful aging, and mortality: the PolSenior study

BackgroundIn the elderly, chronic low-grade inflammation (inflammaging) is a risk factor for the development of aging-related diseases and frailty. Using data from several thousand Eastern Europeans aged 65 years and older, we investigated whether the serum levels of two proinflammatory factors, interleukin-6 (IL-6) and C-reactive protein (CRP), were associated with physical and cognitive performance, and could predict mortality in successfully aging elderly.ResultsIL-6 and CRP levels systematically increased in an age-dependent manner in the entire study group (IL-6: n = 3496 individuals, p < 0.001 and CRP: n = 3632, p = 0.003), and in the subgroup of successfully aging individuals who had never been diagnosed with cardiovascular disease, myocardial infarction, stroke, type 2 diabetes, or cancer, and had a Mini Mental State Examination (MMSE) score ≥24 and a Katz Activities of Daily Living (ADL) score ≥5 (IL-6: n = 1258, p < 0.001 and CRP: n = 1312, p < 0.001). In the subgroup of individuals suffering from aging-related diseases/disability, only IL-6 increased with age (IL-6: n = 2238, p < 0.001 and CRP: n = 2320, p = 0.249). IL-6 and CRP levels were lower in successfully aging individuals than in the remaining study participants (both p < 0.001). Higher IL-6 and CRP levels were associated with poorer physical performance (lower ADL score) and poorer cognitive performance (lower MMSE score) (both p < 0.001). This association remained significant after adjusting for age, gender, BMI, lipids, estimated glomerular filtration rate, and smoking status. Longer survival was associated with lower concentrations of IL-6 and CRP not only in individuals with aging-related diseases/disability (HR = 1.063 per each pg/mL, 95 % CI: 1.052-1.074, p < 0.001 and HR = 1.020 per each mg/L, 95 % CI: 1.015-1.025, p < 0.001, respectively) but also in the successfully aging subgroup (HR = 1.163 per each pg/mL, 95 % CI: 1.128-1.199, p < 0.001 and HR = 1.074 per each mg/L, 95 % CI: 1.047-1.100, p < 0.001, respectively). These associations remained significant after adjusting for age, gender, BMI, lipids and smoking status. The Kaplan-Meier survival curves showed similar results (all p < 0.001).ConclusionsBoth IL-6 and CRP levels were good predictors of physical and cognitive performance and the risk of mortality in both the entire elderly population and in successfully aging individuals.

FEATURES OF REGULATION OF ERYTHROPOIESIS IN PATIENTS WITH CHRONIC KIDNEY DISEASE STAGE 5D

The aim: to study features of the cytokine profile in patients with chronic kidney disease receiving treatment by programmed hemodialysis. Materials and methods: the study included 100 patients aged 53,4 ± 15,8 years with chronic kidney disease stage 5D, receiving hemodialysis. All patients were performed a detailed interview to clarify the clinical and anamnestic data, features of pharmacotherapy, physical examination, and complex laboratory research, which included hemogram, biochemical analysis of blood to definition of parameters of kidney function, protein, electrolytes, minerals and iron metabolism, determining the level of interleukin-3 and interleukin-6. Results: anemia was found in 89% of patients, had a normocytic normochromic character with elements of anisocytosis. The most severe anemia was associated with a lower dose of erythropoietin and iron, used in the last month. Interleukin-3 averaged 32,8 ± 8,3 pg / ml, minimum 15 pg / ml, maximum 56 pg / ml, which exceeded reference limits. When comparing the levels of interleukin-3 and erythropoietin dose differing vectors of these parameters in patients with anemia of varying severity were indicated. The correlations between the level of interleukin-3 and the fluctuation of the dose of erythropoietin in the last year (r = 0,54; p = 0,01) in patients with mild anemia, and the level of soluble transferrin receptor (r = 0, 84; p = 0,04) in patients with severe anemia were found. The level of interleukin-6 was also higher than the reference values and amounted to 64,6 ± 8,7 pg / ml, the lowest — 36,0 pg / ml, the most — 86,0 pg / ml. The patients with a high risk of systemic inflammation on the scale of Glasgow Prognostic Score had lower levels of interleukin-6. Conclusions: high levels of interleukin-3 and interleukin-6 were revealed in all patients identified. Inverse relationship of interleukin-3 and dose of erythropoietin in depend of severity of anemia was shown. The high risk of systemic inflammation associated with a lower concentration of interleukin-6, which does not allow its use as a universal marker of inflammation in patients with chronic kidney disease receiving hemodialysis.

The role of CXCL10 in the pathogenesis of experimental septic shock.

IntroductionThe chemokine CXCL10 is produced during infection and inflammation to activate the chemokine receptor CXCR3, an important regulator of lymphocyte trafficking and activation. The goal of this study was to assess the contributions of CXCL10 to the pathogenesis of experimental septic shock in mice.MethodsSeptic shock was induced by cecal ligation and puncture (CLP) in mice resuscitated with lactated Ringer’s solution and, in some cases, the broad spectrum antibiotic Primaxin. Studies were performed in CXCL10 knockout mice and mice treated with anti-CXCL10 immunoglobulin G (IgG). Endpoints included leukocyte trafficking and activation, core body temperature, plasma cytokine concentrations, bacterial clearance and survival.ResultsCXCL10 was present at high concentrations in plasma and peritoneal cavity during CLP-induced septic shock. Survival was significantly improved in CXCL10 knockout (CXCL10KO) mice and mice treated with anti-CXCL10 IgG compared to controls. CXCL10KO mice and mice treated with anti-CXCL10 IgG showed attenuated hypothermia, lower concentrations of interleukin-6 (IL-6) and macrophage inhibitory protein-2 (MIP-2) in plasma and lessened natural killer (NK) cell activation compared to control mice. Compared to control mice, bacterial burden in blood and lungs was lower in CXCL10-deficient mice but not in mice treated with anti-CXCL10 IgG. Treatment of mice with anti-CXCL10 IgG plus fluids and Primaxin at 2 or 6 hours after CLP significantly improved survival compared to mice treated with non-specific IgG under the same conditions.ConclusionsCXCL10 plays a role in the pathogenesis of CLP-induced septic shock and could serve as a therapeutic target during the acute phase of septic shock.

Retinoic acid suppresses growth of lesions, inhibits peritoneal cytokine secretion, and promotes macrophage differentiation in an immunocompetent mouse model of endometriosis

To determine the effects of all-trans-retinoic acid (RA) on establishment and growth of endometrial lesions, peritoneal interleukin-6 (IL-6) and macrophage chemotactic factor-1 (MCP-1) concentrations, and CD38, CD11b, and F4/80 expression on peritoneal macrophages in an immunocompetent mouse model of endometriosis. Experimental transplantation study using mice. Academic medical center. C57BL/6 recipient mice and syngeneic green fluorescent protein transgenic (GFP+) mice. Recipient mice were inoculated with GFP+ minced uterine tissue to induce endometriosis and treated with RA (400 nmol/day) or vehicle for 17 days (3 days before to 14 days after tissue injection). Total number of GFP+ implants in recipient mice, number of implants showing visible blood vessels, total volume of established lesions per mouse, concentrations of IL-6 and MCP-1 in peritoneal fluid, and expression of CD11b, F4/80, and CD38 on peritoneal macrophages. Retinoic acid treatment for 17 days reduced the number of implants versus controls and decreased the frequency of lesions with vessels. Peritoneal washings in RA-treated animals had lower concentrations of IL-6 and MCP-1 than controls 3 days after endometrial inoculation and lower levels of IL-6 on day 14 after inoculation. Concomitant with these effects on day 14, CD38, CD11b, and F4/80 were higher on macrophages from RA-treated mice versus controls. The development of endometriotic implants is inhibited by RA. This effect may be caused, at least in part, by reduced IL-6 and MCP-1 production and enhanced differentiation of peritoneal macrophages.

Dietary choline and betaine intakes in relation to concentrations of inflammatory markers in healthy adults: the ATTICA study

Background:Choline and betaine are found in a variety of plant and animal foods and were recently shown to be associated with decreased homocysteine concentrations. Objective:The scope of this work was to investigate the associations between dietary choline and betaine consumption and various markers of low-grade systemic inflammation. Design:Under the context of a cross-sectional survey that enrolled 1514 men (18–87 y of age) and 1528 women (18–89 y of age) with no history of cardiovascular disease (the ATTICA Study), fasting blood samples were collected and inflammatory markers were measured. Dietary habits were evaluated with a validated food-frequency questionnaire, and the intakes of choline and betaine were calculated from food-composition tables. Results:Compared with the lowest tertile of choline intake (<250 mg/d), participants who consumed >310 mg/d had, on average, 22% lower concentrations of C-reactive protein (P < 0.05), 26% lower concentrations of interleukin-6 (P < 0.05), and 6% lower concentrations of tumor necrosis factor-α (P < 0.01). Similarly, participants who consumed >360 mg/d of betaine had, on average, 10% lower concentrations of homocysteine (P < 0.01), 19% lower concentrations of C-reactive protein (P < 0.1), and 12% lower concentrations of tumor necrosis factor-α (P < 0.05) than did those who consumed <260 mg/d. These findings were independent of various sociodemographic, lifestyle, and clinical characteristics of the participants. Conclusions:Our results support an association between choline and betaine intakes and the inflammation process in free-eating and apparently healthy adults. However, further studies are needed to confirm or refute our findings.

Components of the mediterranean-type food pattern and serum inflammatory markers among patients at high risk for cardiovascular disease

To evaluate associations between components of the Mediterranean diet and circulating markers of inflammation in a large cohort of asymptomatic subjects at high risk for cardiovascular disease. A total of 339 men and 433 women aged between 55 and 80 years at high cardiovascular risk because of presence of diabetes or at least three classical cardiovascular risk factors, food consumption was determined by a semi-quantitative food frequency questionnaire. Serum concentrations of high-sensitivity C-reactive protein (CRP) were measured by immunonephelometry and those of interleukin-6 (IL-6), intracellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) by enzyme-linked immunosorbent assay. After adjusting for age, gender, body mass index, diabetes, smoking, use of statins, non-steroidal antiinflammatory drugs and aspirin, a higher consumption of fruits and cereals was associated with lower concentrations of IL-6 (P for trend 0.005;both). Subjects with the highest consumption of nuts and virgin olive oil showed the lowest concentrations of VCAM-1, ICAM-1, IL-6 and CRP; albeit only for ICAM-1 was this difference statistically significant in the case of nuts (for trend 0.003) and for VCAM-1 in the case of virgin olive oil (P for trend 0.02). Participants with higher adherence to the Mediterranean-type diet did not show significantly lower concentrations of inflammatory markers (P<0.1 for VCAM-1 and ICAM-1). The consumption of some typical Mediterranean foods (fruits, cereals, virgin olive oil and nuts) was associated with lower serum concentrations of inflammatory markers especially those related to endothelial function, in subjects with high cardiovascular risk living in a Mediterranean country.