Interleukin-6 Concentrations Research Articles

Osteoprotegerin and Inflammation in Incident Peritoneal Dialysis Patients.

Objectives: Osteoprotegerin (OPG) is a member of the tumor necrosis factor receptor family involved in processes in many inflammatory states. OPG concentration is enhanced in the majority of chronic kidney disease (CKD) patients and those undergoing renal replacement therapy. The aim of the study was to assess the relation of OPG and chronic inflammation in peritoneal dialysis (PD) patients and to evaluate whether OPG concentrations in plasma and dialysate were related to plasma and dialysate levels of proinflammatory mediators (interleukin 6 (IL-6), high-sensitivity C-reactive protein (hsCRP), interleukin 33 (IL-33) and interleukin 1 receptor-like 1IL-1RL1 (IL-1RL1, sST2)). Methods: The study included 37 patients of the Peritoneal Dialysis Center, Department of Nephrology, Transplantology and Internal Medicine, Szczecin, Poland, 4-6 weeks after the onset of peritoneal dialysis therapy. During a peritoneal equilibration test, plasma (at 2 h) and dialysate (at 4 h) OPG, IL-33, 1IL-1RL1 (sST2), IL-6 and hsCRP concentrations were determined. Results: Plasma concentration of OPG did not correlate with dialysate OPG level (Rs = 0.04, p = 0.8). There was a strong positive correlation between plasma OPG concentrations and plasma IL-1RL1 (sST2) (Rs = 0.41; p = 0.01), plasma IL-6 (Rs = 0.38; p = 0.01) and plasma hsCRP (Rs = 0.35; p = 0.02). Dialysate OPG concentrations were positively associated with dialysate IL-1RL1 (sST2) (Rs = 0.37; p = 0.02) and dialysate IL-6 levels (Rs = 0.44; p = 0.005). Multivariate analysis showed that higher IL-1RL1 (sST2) (ß = +0.38, p = 0.006), higher plasma hsCRP (ß = +0.32, p = 0.02) and older age (ß = +0.35, p = 0.01) were independent determinants of higher plasma OPG concentration and that higher concentrations of dialysate IL-6 (ß = +0.37, p = 0.02) were independent determinants of higher dialysate OPG concentration. Conclusions: Both plasma and dialysate OPG levels are associated with the severity of systemic and local inflammation illustrated by the plasma and dialysate concentrations of IL-1RL1 (sST2), hsCRP and IL-6, suggesting that OPG might have a pivotal role in explaining the milieu of systemic and intraperitoneal inflammation.

Interleukin-6 and Lymphocyte-to-Monocyte Ratio Indices Identify Patients with Intrahepatic Cholangiocarcinoma.

Intrahepatic cholangiocarcinoma (iCCA) is a fatal biliary tract cancer with a dismal prognosis due to ineffective diagnostic tools with limited clinical utility. This study investigated peripheral blood indices and cytokine levels to diagnose iCCA. Blood samples were collected from healthy subjects (n = 48) and patients with advanced-stage iCCA (n = 47) during a phase I and then phase II trial, respectively. Serum cytokines were measured using a flow cytometer. The peripheral blood indices were estimated based on laboratory data. Multi-linear regression analysis was applied, followed by a probability transformation. The cut-off value and model accuracy were determined using the receiver operating curve (ROC) and the area under the curve (AUC). The interleukin-6 (IL6) and lymphocyte-to-monocyte ratio (LMR) were potential predictors of iCCA [AUC = 0.91 (0.85-0.97) and 0.81 (0.68-0.93); sensitivity = 0.70 and 0.91; specificity = 0.91 and 0.85, respectively]. Patients with IL6 concentrations higher than 11.635 pg/mL (OR = 23.33, p < 0.001) or LMR lower than 7.2 (OR = 58.08, p < 0.001) are at risk of iCCA development. Patients with IL6 levels higher than 21.83 pg/mL, between 15.95 and 21.83 pg/mL, between 8.8 and 15.94 pg/mL, and lower than 8.8 pg/mL were classified as very high-, high-, intermediate-, and low-risk, respectively. Patients with an LMR between 1 and 3.37, 3.38 and 5.76, 5.77 and 7.18, and higher than 7.18 were classified as very high-, high-, intermediate-, and low-risk, respectively. LMR is recommended for iCCA screening since the estimation is based on a routine laboratory test, which is available in most hospitals.

A mouse model of chronic primary pain that integrates clinically relevant genetic vulnerability, stress, and minor injury.

Chronic primary pain conditions (CPPCs) affect over 100 million Americans, predominantly women. They remain ineffectively treated, in large part because of a lack of valid animal models with translational relevance. Here, we characterized a CPPC mouse model that integrated clinically relevant genetic (catechol-O-methyltransferase; COMT knockdown) and environmental (stress and injury) factors. Compared with wild-type mice, Comt+/- mice undergoing repeated swim stress and molar extraction surgery intervention exhibited pronounced multisite body pain and depressive-like behavior lasting >3 months. Comt+/- mice undergoing the intervention also exhibited enhanced activity of primary afferent nociceptors innervating hindpaw and low back sites and increased plasma concentrations of norepinephrine and pro-inflammatory cytokines interleukin-6 (IL-6) and IL-17A. The pain and depressive-like behavior were of greater magnitude and longer duration (≥12 months) in females versus males. Furthermore, increases in anxiety-like behavior and IL-6 were female-specific. The effect of COMT genotype × stress interactions on pain, IL-6, and IL-17A was validated in a cohort of 549 patients with CPPCs, demonstrating clinical relevance. Last, we assessed the predictive validity of the model for analgesic screening and found that it successfully predicted the lack of efficacy of minocycline and the CB2 agonist GW842166X, which were effective in spared nerve injury and complete Freund's adjuvant models, respectively, but failed in clinical trials. Yet, pain in the CPPC model was alleviated by the beta-3 adrenergic antagonist SR59230A. Thus, the CPPC mouse model reliably recapitulates clinically and biologically relevant features of CPPCs and may be implemented to test underlying mechanisms and find new therapeutics.

Reduction of mortality, cardiac damage, and cerebral damage by IL-1 inhibition in a murine model of TTP

AbstractThrombotic thrombocytopenic purpura (TTP), a rare but fatal disease if untreated, is due to alteration in von Willebrand factor cleavage resulting in capillary microthrombus formation and ischemic organ damage. Interleukin-1 (IL-1) has been shown to drive sterile inflammation after ischemia and could play an essential contribution to postischemic organ damage in TTP. Our objectives were to evaluate IL-1 involvement during TTP and to test the efficacy of the recombinant IL-1 receptor antagonist, anakinra, in a murine TTP model. We retrospectively measured plasma IL-1 concentrations in patients with TTP and controls. Patients with TTP exhibited elevated plasma IL-1α and -1β concentrations, which correlated with disease course and survival. In a mouse model of TTP, we administered anakinra (IL-1 inhibitor) or placebo for 5 days and evaluated the efficacy of this treatment. Anakinra significantly reduced mortality of mice (P < .001). Anakinra significantly decreased TTP-induced cardiac damage as assessed by blood troponin concentrations, evaluation of left ventricular function by echocardiography, [18F]fluorodeoxyglucose positron emission tomography of myocardial glucose metabolism, and cardiac histology. Anakinra also significantly reduced brain TTP-induced damage evaluated through blood PS100b concentrations, nuclear imaging, and histology. We finally showed that IL-1α and -1β trigger endothelial degranulation in vitro, leading to the release of von Willebrand factor. In conclusion, anakinra significantly reduced TTP mortality in a preclinical model of the disease by inhibiting both endothelial degranulation and postischemic inflammation, supporting further evaluations in humans.

Expression of IL-4 and IL-12 in the aqueous humor of patients with chronic primary angle-closure glaucoma.

Angle-closure glaucoma is a common type of glaucoma in Asian populations. However, the role of inflammatory cytokines in angle-closure glaucoma is yet to be elucidated. Therefore, this study aimed to examine the expression of interleukin-4 (IL-4) and IL-12 in the aqueous humor of patients with chronic primary angle-closure glaucoma (CPACG) and elucidate the correlations between IL-4 and IL-12 concentrations in the aqueous humor, the degree of visual field defects, and retinal nerve fiber layer (RNFL) thickness in patients with CPACG. Aqueous humor samples were obtained from 31 patients diagnosed with CPACG at the Shaoxing People's Hospital between April 2022 and March 2023 and from 30 individuals with cataract (control). Based on the degree of the mean defect (MD), patients were divided into three groups: group A (MD ≤ -6dB, n= 10), group B (-6dB< MD< -12dB, n= 9), and group C (MD ≥ - 12dB, n= 12). RNFL thickness was measured using an optical coherence tomograph, and the concentrations of IL-4 and IL-12 in the aqueous humor were measured using Luminex technology. Aqueous humor concentration of IL-4 was significantly higher (p = 0.036) in the CPACG group than in the cataract group. However, there was no significant difference (p > 0.05) in IL- 12 concentration between the two groups. Additionally, there were no significant differences (p > 0.05) in IL-4 and IL-12 levels among patients with varying degrees of visual field defects (groups A, B, and C). Spearman's correlation analysis showed that IL-4 and IL-12 concentrations were not correlated (p > 0.05) with RNFL thickness around the optic disc and the degree of visual field defects. Conclusively, IL-4 may play an important role in the pathogenesis of CPACG. Given that IL-4 and IL-12 concentrations in the aqueous humor were not significantly correlated with RNFL thickness and the degree of visual field defects, the increase in IL-4 and IL-12 expression may not induce apoptosis and loss of retinal ganglion cells or affect RNFL thickness as well as the degree of visual field defects.

Assessment of the functional state of gut microbiota in patients with metabolic-associated fatty liver disease in combination with type 2 diabetes mellitus

Background. The purpose of the study was to assess the functional state of gut microbiota in patients with metabolic-associated fatty liver disease (MAFLD) combined with type 2 diabetes mellitus (T2DM). Materials and methods. The prospective interventional randomized study included 71 patients with MAFLD in combination with T2DM, who were examined and divided into the 2 groups. The first group included 39 people with MAFLD and T2DM without small intestinal bacterial overgrowth (SIBO). The second group consisted of 32 patients with MAFLD in combination with T2DM and SIBO. The control group included 25 practically healthy patients. The content of serum zonulin was determined by enzyme-linked immunosorbent assay (ELISA) using test systems IDK Zonulin ELISA, KR5601. Serum concentration of interleukin (IL) 6 and IL-10 was assessed by the ELISA method using the Human Interleukin 6 and 10 ELISA Kit test systems. The content of short-chain fatty acids in feces was determined by gas chromatography with mass spectrometry in the PerkinElmer Clarus 680 GC Gas Chromatograph. Results. Patients of the first and second groups had an increase in hepatic aminotransferases, total cholesterol, triglycerides, fasting blood glucose, insulin, HOMA-IR, glycosylated hemoglobin, serum zonulin, leptin, IL-6 and liver attenuation coefficient and a decrease in high-density lipoprotein. The results of steatometry revealed a severe degree of hepatic steatosis (S3) in patients with MAFLD combined with T2DM and SIBO and without SIBO. During the quantitative study of the level of butyric acid in feces, it was found to be significantly reduced, by 2.3 times in the first group and by 3.4 times in the second one, compared to the controls (p &lt; 0.001). The content of butyric acid was decreased by 1.4 times in the second group compared to the first one (p &lt; 0.001). When evaluating the level of acetic acid, it was found to be significantly increased compared to the controls, by 1.2 times in the first group and by 1.3 times in the second one (p &lt; 0.001). The concentration of propionic acid was increased by 1.3 times in the first group and by 1.5 times in the second one compared the control group (p &lt; 0.05). When comparing the level of acetic acid, a significant increase by 1.3 times was observed in patients of the first and second groups compared to patients of the control group (p &lt; 0.001). The content of propionic and acetic acids was increased by 1.1 times in the second group compared to patients of the first group (p &lt; 0.05). When analyzing the correlation coefficients in patients with MAFLD combined with T2DM and SIBO and without SIBO, a direct proportional strong correlation was revealed between the levels of butyric, acetic and propionic acids and serum zonulin, IL-6, IL-10. A direct moderate correlation was found between the content of short-chain fatty acids and leptin, indicators of lipid metabolism (total cholesterol, triglycerides), carbohydrate metabolism (fasting blood glucose, HOMA-IR, HbA1c) and inverse weak correlation with high-density lipoprotein. A direct moderate correlation was revealed between levels of short-chain fatty acids and indicators of functional activity of the liver (alanine aminotransferase, aspartate aminotransferase), liver attenuation coefficient in patients with MAFLD combined with T2DM and SIBO and without SIBO. Conclusions. Increased intestinal permeability and hyperleptinemia have been found in patients with МAFLD combined with T2DM and SIBO and without SIBO. When studying the functional state of the gut microbiota, an increase was found in propionic and acetic acids and a decrease in butyric acid, which indicates an increase in the number of Bacteroidetes in the intestine and a decrease in Firmicutes. Patients with MAFLD combined with Т2DM and SIBO and without SIBO had a direct proportional strong correlation between the levels of butyric, acetic and propionic acids and serum zonulin, IL-6, IL-10, which is associated with pro-inflammatory and anti-inflammatory processes in the intestinal mucosa and a violation of the permeability of the intestinal barrier. It was found that concentrations of short-chain fatty acids correlate with indicators of functional activity of the liver (alanine aminotransferase, aspartate aminotransferase), leptin, indicators of carbohydrate and lipid metabolism, degree of hepatic steatosis.

Establishment of reference intervals for plasma IL-2, IL-4, IL-5, and IL-17A in healthy adults from the Jiangsu region of eastern China using flow cytometry: A single-center study

BackgroundCytokines are of utmost importance in both the physiological and pathological immune responses of the human body. This study utilized flow cytometry to measure the levels of plasma interleukin-2 (IL-2), interleukin-4 (IL-4), interleukin-5 (IL-5) and interleukin-17A (IL-17A) and established their reference intervals, aiming to provide data support for the diagnosis and treatment of clinical diseases. MethodsAccording to the inclusion and exclusion criteria, a total of 728 reference individuals were included in this study from January 2023 to June 2023. The Kolmogorov–Smirnov test was used to analyse the distributions of plasma IL-2, IL-4, IL-5 and IL-17A. The reference intervals of plasma IL-2, IL-4, IL-5 and IL-17A were established by the unilateral percentile method (95th percentile) based on the guidelines of C28-A 3 and WS/T 402–2012. ResultsIn this study, the levels of plasma IL-2, IL-4, IL-5 and IL-17A were nonnormally distributed. The concentrations of plasma IL-2, IL-4, IL-5 and IL-17A in healthy adults were not significantly different by sex or age (all P > 0.05). Therefore, all the reference individuals were combined into one group, and the reference intervals of plasma IL-2, IL-4, IL-5 and IL-17 were established by flow cytometry (IL-2 ≤ 10.25 pg/mL, IL-4 ≤ 9.87 pg/mL, IL-5 ≤ 3.36 pg/mL and IL-17A ≤ 9.46 pg/mL). ConclusionsWe first established the reference intervals of plasma IL-2, IL-4, IL-5 and IL-17A in healthy adults based on a single-center population in the Jiangsu region in eastern China, which will provide an important reference value for evaluating human immune status and the diagnosis and treatment of clinical diseases.

Interleukin-6 as a Milk Marker of Clinical and Subclinical Intramammary Infections (IMI) in Cows Caused by Streptococcus spp.

The aim of the study was to evaluate the concentrations of Interleukin-6 (IL-6) in milk and serum of healthy cows (HE) and cows with mastitis caused by Streptococcus spp. The blood and milk samples were obtained from Holstein-Friesian cows (Lublin region, Poland). A total of 43 milk and serum samples from 28 cows with mastitis and 15 healthy cows were selected for study. IL-6 levels in milk from HE cows ranged from 6.09-80.24 pg/mL (median 26.6 pg/mL) and were significantly lower than in milk from both cows with clinical and subclinical mastitis (487.09 pg/mL vs. 26.6 pg/mL in CM, p < 0.001; and 165.31 pg/mL vs. 26.6 pg/mL in SCM, p < 0.001). The IL-6 concentration in the serum of HE was not significantly different from the serum IL-6 of the entire group of mastitis cows, regardless of whether the inflammation proceeded in a clinical or subclinical form (44.37 pg/mL vs. 78.09 pg/mL; 128.29 pg/mL vs. 78.09 pg/mL, respectively). The present study indicates that cows with mastitis caused by Streptococcus spp. develop a local immune response in the mammary gland in response to the pathogen. Monitoring of IL-6 levels in milk can allow early detection of mastitis, which is especially important in cases of subclinical inflammation.

Association of multiple metabolic and cardiovascular markers with the risk of cognitive decline and mortality in adults with Alzheimer's disease and AD-related dementia or cognitive decline: a prospective cohort study.

There is a scarcity of data stemming from large-scale epidemiological longitudinal studies focusing on potentially preventable and controllable risk factors for Alzheimer's disease (AD) and AD-related dementia (ADRD). This study aimed to examine the effect of multiple metabolic factors and cardiovascular disorders on the risk of cognitive decline and AD/ADRD. We analyzed a cohort of 6,440 participants aged 45-84 years at baseline. Multiple metabolic and cardiovascular disorder factors included the five components of the metabolic syndrome [waist circumference, high blood pressure (HBP), elevated glucose and triglyceride (TG) concentrations, and reduced high-density lipoprotein cholesterol (HDL-C) concentrations], C-reactive protein (CRP), fibrinogen, interleukin-6 (IL-6), factor VIII, D-dimer, and homocysteine concentrations, carotid intimal-medial thickness (CIMT), and urine albumin-to-creatinine ratio (ACR). Cognitive decline was defined using the Cognitive Abilities Screening Instrument (CASI) score, and AD/ADRD cases were classified using clinical diagnoses. Over an average follow-up period of 13 years, HBP and elevated glucose, CRP, homocysteine, IL-6, and ACR concentrations were significantly associated with the risk of mortality in the individuals with incident AD/ADRD or cognitive decline. Elevated D-dimer and homocysteine concentrations, as well as elevated ACR were significantly associated with incident AD/ADRD. Elevated homocysteine and ACR were significantly associated with cognitive decline. A dose-response association was observed, indicating that an increased number of exposures to multiple risk factors corresponded to a higher risk of mortality in individuals with cognitive decline or with AD/ADRD. Findings from our study reaffirm the significance of preventable and controllable factors, including HBP, hyperglycemia, elevated CRP, D-dimer, and homocysteine concentrations, as well as, ACR, as potential risk factors for cognitive decline and AD/ADRD.

Immunological Assessment of Interleukin-6 in Patients with Gastric (Stomach) Ulceration of Acute and Chronic Types in Babylon Province

Stomach ulcers have emerged as a serious public health concern. Serum interleukin-6 (IL-6) levels in individuals with chronic and acute gastric ulcers will be examined in this study. Sixty blood samples were obtained from participants in the research. The Marjan Teaching Hospital, Al-Sadiq Hospital in Babylon Province, Iraq, treated forty patients having stomach ulcer surgery between March and November 2023; the control group consisted of twenty individuals. A high mean value for IL-6 concentration was seen in both the chronic and acute patient groups compared to the control group (44.1 ± 28.6 pg/ml) for chronic patient and (30.2 ± 15.4 pg/ml) for acute patients with significant differences(P&lt;0.05). The results conducted a noteworthy rise in the level of interleukin-6 in the age group of 71–80 years, with a mean value of 10.9±9.02 pg/ml, compared to other age groups. Additionally, when considering gender, it was observed that males had a higher mean value of 73.4±30.60 pg/ml, while females had a similar mean value of 73.4±30.60 pg/ml. These findings were found to be statistically significant (P&lt;0.05).

The Correlation Between Interleukin -6 and Dehydroepiandrosterone Sulfate in Patients with Severe COVID-19

Background: Numerous studies have demonstrated that interleukin-6 (IL-6) and serum dehydroepiandrosterone sulfate levels are negatively correlated. Low DHEA-S levels may be associated with severe disease and clinically ailing patients in the context of infectious diseases. Individuals infected with Coronavirus disease who exhibit elevated levels of IL-6 may undergo a cytokine storm, which can result in severe manifestations and a dismal prognosis. Objectives: To examine the relationship between DHEA-S and Il-6 in patients exhibiting severe manifestations of COVID-19. Subjects and Methods: A case-control investigation with 79 patients, ranging in age from 36 to 74 years, who were admitted to the hospital due to severe COVID-19 disease. A control group of 72 ostensibly healthy individuals was also included in the study. Using the ELISA method, the concentrations of IL-6 and DHEA-S in the serum of both groups were determined. The statistical analyses involved the application of the Pearson correlation coefficient and the T-test. None of the authors present any conflicts of interest. Results: With a Pearson correlation coefficient (r) of -0.8349, the study revealed a highly significant negative correlation (P &lt; 0.0001) between the mean IL-6 level (64.369 pg/ml ± 2.6237) and the mean DHEA-S level (1.2728 ng/ml ± 1.7005) in the study group. An exceptionally significant statistical disparity was also identified when IL-6 and DHEA-S levels were compared between the study and control groups. Conclusions: In severely infected COVID-19 patients inverse correlation between the levels of IL-6 and DHEA-S indicates that DHEA-S deficiency may play a role in cytokine storm formation for these patients.

Interleukin-6 Concentration in Peritoneal Fluid and Serum of Patients with and without Endometriosis

Interleukin-6 Concentration in Peritoneal Fluid and Serum of Patients with and without Endometriosis

Cytokine Genetic Polymorphism of Interleukin-4 and Risk of Asthma in Some Iraqi Patients

Abstract Background: Asthma, a chronic inflammatory respiratory disorder, is influenced by genetic and environmental factors. Allergic asthma is becoming more common because of higher levels of air pollution. Interleukin-4 (IL-4) plays an important role in allergic inflammation and causes the expression of vascular cell adhesion molecule-1. Objective: The present study aims to shed light on the association between cytokine genetic polymorphisms and asthma in Iraqi patients, and to determine their impact on the risk of disease, under the scope of the following: (1) IL-4 cytokines, in terms of their serum level. (2) Assessment of the polymorphisms in the promoter regions of the IL-4, genes in asthma disease patients was carried out, and then their impact on the profile of investigated cytokines was evaluated. Such a collective evaluation may aid in a better understanding of etiopathogenesis in the asthma disease. Materials and Methods: A case-control study was conducted that included 100 participants divided into a patient group (n = 50) with bronchial asthma and a healthy group as a control (n = 50) without asthma. Blood specimens were collected from participants at Marjan Hospital, Babylon Governorate. Serum levels of IL-4 were estimated by an enzyme-linked immunosorbent assay (ELISA) kit. IL4-590 gene polymorphism was detected using amplification refractory mutation system polymerase chain reaction (PCR) with specific primer sequences. Results: The mean concentrations of serum IL-4 were significantly higher in patients having asthma compared to the healthy group (149.84 vs. 53.50, P &lt; 0.0001). In terms of allele and genotype frequencies, the TT genotype was shown to be less common in asthma group compared to controls (4% vs. 22%), whereas the CT genotype was more common in asthma patients (34% vs. 16%). The CC genotype was similar between the two groups. The T allele was more frequent in healthy (39%) compared to asthmatic group (12%), whereas the C allele frequency was higher in asthma patients (61%) compared to controls (88%). Conclusion: This study suggests that gene polymorphism of IL4-590 is associated with risk of developing asthma. Asthma patients have elevated levels of IL-4 and a lower frequency of the TT genotype, indicating an increased likelihood of developing asthma when carrying the T allele and TT genotype. Conversely, the C allele may have a protective influence against asthma development.

Anthocyanins attenuate vascular and inflammatory responses to a high fat high energy meal challenge in overweight older adults: A cross-over, randomised, double-blind clinical trial

Postprandial metabolic imbalances are important indicators of later developing cardiovascular disease (CVD)(1). This study investigated the effects of food anthocyanins on vascular and microvascular function, and CVD associated biomarkers following a high fat high energy (HFHE) meal challenge in overweight older adults. Sixteen subjects (13 female, 3 male, mean age 65.9 SD 6.0 and body mass index 30.6 kg/m 2 SD 3.9) participated in a crossover, randomised, controlled, double-blind clinical trial (Australian New Zealand Clinical Trials Registry # ACTRN12620000437965). Participants consumed a HFHE breakfast meal (65g total fat; 33g saturated fat) together with a 250 mL dose of either intervention (Queen Garnet Plum providing 201 mg anthocyanins) or control (apricot) juice. A wash-out period of 14 days occurred between meal challenges, with a 4-day run-in period for juice consumption before each challenge. Blood samples and blood pressure measures were collected at baseline, 2 h and 4 h following the HFHE meal. Vascular function, assessed using flow mediated dilatation (FMD), and microvascular cutaneous vascular reactivity, measured using Laser Speckle Contrast Imaging (LSCI), were evaluated at baseline and 2 h after the HFHE meal. Participants had a higher 2 h postprandial FMD (+1.14%) and a higher microvascular post-occlusive reactive hyperaemia (+0.10 perfusion units per mmHg) when allocated to the anthocyanin compared to the control arm (P = 0.019 and P = 0.049, respectively). C-reactive protein was lower 4 h postprandially in the anthocyanins (1.80 mg/L, IQR 0.90) vs control arm (2.30 mg/L, IQR 1.95) (P = 0.026), accompanied by a trend for lower concentrations of interleukin-6 (P = 0.075). No significant postprandial differences were observed between treatments for blood pressure, triacylglycerol, total cholesterol, serum derivatives of reactive oxidative metabolites, tumor necrosis factor α, interleukin-1 β, or maximum microvascular perfusion following iontophoresis of acetylcholine. Fruit-based anthocyanins attenuated the potential postprandial detrimental effects of a HFHE challenge on parameters of vascular and microvascular function, and inflammatory biomarkers in overweight older adults. Anthocyanins may reduce cardiovascular risk associated with endothelial dysfunction and inflammatory responses to a typical high fat ‘Western’ meal.

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&lt;0.001 and r=0.297; p&lt;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.

Interactions of humoral immune response indicators and parameters of systemic inflammatory response in patients with post-COVID-19 syndrome

Objective. To assess the state of the systemic inflammatory response and humoral immune response in middle-aged patients came through COVID-19 infection in mild and moderate severity. Materials and methods. A cohort single-center study involving 83 patients came through COVID-19 infection in mild and moderate severity (women - 69.9% (58 patients), men - 30.1% (25 patients); median age 53 years [49; 56] was conducted over the period 2022-2023. All patients underwent clinical examination, evaluation of humoral response with determination of IgG and IgM antibodies to SARS-CoV-2 virus, as well as concentration of interleukins: interleukin-1β, interleukin-4, interleukin-6, interleukin-8, interleukin-10, high-sensitivity C-reactive protein, tumour necrosis factor α, transforming growth factor β1 and procalcitonin concentrations. Patients were divided into three groups: 1-3 months; 3-6 months; and 6 months to 1 year after COVID-19 infection. Results. Within a year the percentage of IgM-positive patients in all patient groups was about a quarter (25 %, 21 % and 25 % respectively). While remaining within the reference values for the whole group, procalcitonin and interleukin-10 levels in the selected cohort exceeded those of the test-negative cohort (p = 0.0053 and p = 0.0044, respectively), which we considered as persistent chronic compensated inflammation. Conclusion. A quarter of patients who came through COVID-19 infection in mild and moderate severity have persistently positive IgM levels for a year, combined with proinflammatory status according to systemic inflammatory response parameters.

The content of lactoferrin and interleukin-8 in breast milk of patients with lactational mastitis

Introduction and aim. Information concerning lactoferrin and interleukin-8 (IL-8) local levels in breast milk are not numerous and requires further research. The aim of this study was to determine the content of lactoferrin and interleukin-8 in the breast milk of patients with lactational mastitis, and to identify new potential markers for assessing the activity of the inflammatory process in the mammary gland. Material and methods. This study analyzed the breast milk of 30 women with lactostasis (group I), 37 women with lactational mastitis (group II) and 30 healthy lactating women (age 26±5 years old). The milk content of lactoferrin and interleukin-8 (IL-8) was determined by enzyme-linked immunosorbent assay. Results. The average value of lactoferrin in breast milk of healthy women was 4.78±0.47 mg/mL, exceeding levels in group I 1.8 times (p&lt;0.05). The level of lactoferrin in group II exceeds the control values 3.1 times (p&lt;0.05). The content of IL-8 in breast milk of women in group I was 7.3 times higher than the control (3.63±0.12 pg/mL, p&lt;0.05). In lactational mastitis, the concentration of IL-8 in breast milk exceeded the group I 13.9 times (p&lt;0.05) and was 1.9 times higher than group I (p&lt;0.05). Conclusion. The analysis has revealed an increase of lactoferrin and IL-8 in breast milk of the test groups, which indicates the activation of non-specific protection.

Engagement with nature and proinflammatory biology

BackgroundPrior evidence indicates that contact with nature improves physical health, but data explicitly linking engagement with nature to biological processes are limited. DesignLeveraging survey and biomarker data from 1,244 adults (mean age = 54.50 years, range = 34–84 years) from the Midlife in the United States (MIDUS II) study, we examined associations between nature engagement, operationalized as the frequency of pleasant nature encounters, and systemic inflammation. Concentrations of interleukin-6 (IL-6), C-reactive protein (CRP), and fibrinogen were measured from fasting blood samples. Analyses adjusted for sociodemographic, health behavior, and psychological well-being covariates. ResultsMore frequent positive nature contact was independently associated with lower circulating levels of inflammation. ConclusionsThese findings add to a growing literature on the salubrious health effects of nature by demonstrating how such experiences are instantiated in downstream physiological systems, potentially informing future interventions and public health policies.

Increased interleukin-6 is associated with higher risk of heart failure in people with type 2 diabetes.

We aimed to determine the association between serum interleukin-6 (IL-6) concentrations and new-onset heart failure (HF) in persons with type 2 diabetes (T2D). We performed a case-control study nested in the Diabetes Care System Cohort, a prospective cohort of persons with T2D in primary care. We included 724 participants, of whom 141 developed HF during 5years of follow-up and 583 were age- and sex-matched controls. IL-6 was measured at baseline and categorized into four groups: Group 1 was composed of participants with IL-6 below the detection limit of 1.5pg/mL, and the remainder were divided into tertiles. We performed logistic regression analyses with categorized IL-6 or continuous IL-6 as the determinant and new-onset HF as the outcome adjusted for follow-up time, age, sex, glycated haemoglobin, estimated glomerular filtration rate, albumin/creatinine ratio, and cardiovascular disease at baseline. Effect modification by sex was tested. Participants were 70.7±9.0years, and 38% were women. In comparison with Group 1, all tertiles were associated with an increased risk of HF with odds ratios of 2.1 [95% confidence interval (CI): 1.2-2.9], 2.8 (95% CI: 2.0-3.7), and 2.1 (95% CI: 1.3-3.0), respectively, for Tertiles 1-3. Continuous IL-6 was associated with the development of HF with an odds ratio of 1.2 (95% CI: 1.0-1.5). No effect modification by sex was observed. Higher IL-6 levels are associated with the development of HF in persons with T2D. Further research should determine whether IL-6-lowering interventions could prevent the development of HF.

Ameliorative Effect of Naringenin in 5-Fluorouracil-Induced Hepatotoxicity: An Experimental Study on Albino Wistar Rats

Background: Hepatotoxicity is an adverse complication in 5-Fluorouracil cancer treatment. Inflammation, oxidative stress, apoptosis and DNA damage are essential in the pathogenesis of liver damage. The present study evaluated the ameliorative effect of Naringenin (NG) in 5-FU at two different intervals in hepatic damage. Methods: Total (n=48) Albino Wistar rats were divided into 4 groups (N=12), Control-normal saline (group-1) per oral, 5-FU (group-2) @ 20 mg/kg b.wt was injected intraperitoneal (IP) for first 5 days, NG (group-3) @100 mg/kg b. wt/day orally for 28 days. Another group-4 was concurrently treated with NG along with 5-FU for 28 days and sacrificed on the 14th and 28th day of the experiment. Result: On exposure to 5-FU, biochemical variation of liver enzymes (ALT, AST, ALP and TP) were significantly increased while NG treatment significantly reduced these biomarkers in group 2 on 14th day and 28th day of the experiment. Furthermore, NG treatment significantly reduced lipid peroxidation and increases the antioxidant profile. It also significantly reduced elevated concentrations of pro-inflammatory cytokines like tumour necrosis factor (TNF-α), interleukin -1β (IL-1β), interleukin-6 (IL-6) with increased concentrations of interleukin-10 (IL-10) along with reduced immunohistochemical expression of nuclear factor kappa light chain enhancer of activated B cells (NF-κB) and Caspases -3 (Cas-3) by NG. On histopathology, pathological lesions were observed to support biochemical variations in group-2 rats. In group-4 rats, NG ameliorates liver enzymes, inflammatory cytokines and oxidative indices through an anti-oxidant, anti-inflammatory and anti-apoptotic property.