Interleukin-6 Concentrations Research Articles

The Utility of Noninvasive Urinary Biomarkers for the Evaluation of Vesicoureteral Reflux in Children.

Vesicoureteral reflux (VUR) is one of the most important disorders encountered in pediatric nephrology due to its frequency and potential evolution to chronic kidney disease (CKD). The aim of our study was to identify noninvasive and easy-to-determine urinary markers to facilitate the diagnosis and staging of VUR. We performed a cross-section study including 39 patients with VUR followed over three years (August 2021-September 2023) and 39 children without urinary disorder (the control group). We measured the urinary concentration of interleukin-6 (IL-6), cathelicidin (LL-37), and neutrophil gelatinase-associated lipocalin (NGAL) in VUR and healthy controls. Moreover, we analyzed the correlation between these biomarkers and the presence of renal scars (RS), reflux nephropathy (RN), and CKD. The NGAL concentrations were significantly higher in patients with VUR than in the controls (p = 0.02). Regarding the severity of the reflux, NGAL/creatinine and LL-37/creatinine were positively correlated with severe reflux (p = 0.04, respectively, p = 0.02). In patients with VUR and RS, LL-37/creatinine was significantly lower (p = 0.01). LL-37/creatinine with an AUC of 0.71 and NGAL/creatinine with an AUC of 0.72 could be acceptable diagnostic tests for severe VUR. In conclusion, urinary IL-6, NGAL, and LL-37 could serve as valuable markers for diagnosing and predicting outcomes in patients with VUR and RN.

Concentrations of serum amyloid A, haptoglobin and some cytokines in calves with Cryptosporidiosis in the pre- and post-treatment stage

This study aims to determine serum amyloid A (SAA), haptoglobin (Hp), interleukin-1β (IL-1β), interleukin 6 (IL-6) and tumor necrosis factor-α (TNF-α) concentration in cases of Cryptosporidiosis that are frequently encountered in calves in veterinary medicine. Although many experimental studies have been conducted in this field, studies of naturally infected calves are quite a few. In this study, 10 neonatal Holstein calves diagnosed with Cryptosporidium were included. Stool samples were taken from calves with diarrhea using a rapid test kit (BIO-K 313 rapid test kit). Blood samples were obtained from the jugular vein pre- and post-treatment for biochemical measurements. SAA, Hp, IL-1β, IL-6 and TNF-α concentration measurements were conducted with ELISA reader using commercial kits. Calves with Cryptosporidiosis presenting with diarrhea showed a statistical difference in SAA, Hp, IL-1β, IL-6, white blood cell and hemoglobin values before and after treatment, whereas hematocrit, red blood cell and TNF-α concentrations did not show any statistical difference before and after treatment. According to these findings, to follow up the treatment process of calves with Cryptosporidiosis, it is thought that measuring the concentration of SAA, Hp, IL-1β and IL-6 will be useful for determining disease severity, selecting appropriate treatment, following treatment efficacy and determining subclinical diseases.

Ningmitai capsule improves the semen quality of male infertile with chronic prostatitis by antioxidant and anti-inflammatory

Aim: To observe the effects of Ningmitai capsule on semen parameters of infertile patients with chronic prostatitis (CP) and explore the mechanisms. Methods: A total of 43 patients diagnosed with CP were included in the study and administered Ningmitai capsules (4 capsules per dose) for a duration of 6 weeks. Subsequently, assessments were conducted on parameters including sperm concentration, forward progressive motility, total motility, oxidative and anti-oxidative indicators, as well as the concentration of interleukin-8 (IL-8) in seminal plasma before and after the treatment period. Results: Compared to pre-treatment, forward progressive motility and total motility of the semen increased significantly (37.15% ± 18.77% vs. 45.44% ± 19.08%, P < 0.05 and 42.56% ± 21.22% vs. 51.64% ± 19.48%, P < 0.05). And the expression of superoxide dismutase (SOD) and total antioxidant capacity (T-AOC) increased significantly after treatment as well (11.36 μmol/L ± 3.28 μmol/L vs. 12.79 μmol/L ± 2.87 μmol/L, P < 0.05 and 9.34 U/mL ± 3.22 U/mL vs. 11.21 U/mL ± 4.87 U/mL, P < 0.05). In addition, the expression of malondialdehyde (MDA) and IL-8 decreased significantly after treatment (41.06 μmol/L ± 24.39 μmol/L vs. 32.17 μmol/L ± 15.04 μmol/L, P < 0.05 and 79.69 ng/L ± 26.24 ng/L vs. 61.35 ng/L ± 23.41 ng/L, P < 0.05). No significant difference in sperm concentration and sperm DNA fragmentation index was observed after the treatment (P > 0.05). Conclusions: Ningmitai capsule can enhance the antioxidant capacity and down-regulate the expression of cytokines in the semen, thereby improving the semen parameters of infertile patients with CP.

Temporal dynamics of pro-inflammatory cytokines and serum corticosterone following acute sleep fragmentation in male mice.

Obstructive sleep apnea is increasing worldwide, leading to disordered sleep patterns and inflammatory responses in brain and peripheral tissues that predispose individuals to chronic disease. Pro-inflammatory cytokines activate the inflammatory response and are normally regulated by glucocorticoids secreted from adrenal glands. However, the temporal dynamics of inflammatory responses and hypothalamic-pituitary-adrenal (HPA) axis activation in relation to acute sleep fragmentation (ASF) are undescribed. Male C57BL/6J mice were exposed to ASF or control conditions (no ASF) over specified intervals (1, 2, 6, or 24 h) and cytokine gene expression (IL-1β, TNF-α) in brain and peripheral tissues as well as serum glucocorticoid and interleukin-6 (IL-6) concentration were assessed. The HPA axis was rapidly activated, leading to elevated serum corticosterone from 1-24 h of ASF compared with controls. This activation was followed by elevated serum IL-6 concentration from 6-24 h of ASF. The tissue to first exhibit increased pro-inflammatory gene expression from ASF was heart (1 h of ASF). In contrast, pro-inflammatory gene expression was suppressed in hypothalamus from 1 h of ASF, but elevated at 6 h. Because the HPA axis was activated throughout ASF, this suggests that brain, but not peripheral, pro-inflammatory responses were rapidly inhibited by glucocorticoid immunosuppression.

Serum concentrations of proinflammatory biomarker interleukin-6 (IL-6) as a predictor of postoperative complications after elective colorectal surgery

BackgroundThe aim of this prospective study was to evaluate the role of serum IL-6 as a potential predictive biomarker of postoperative complications (POC) in elective colorectal surgery.MethodA total of 115 patients underwent colorectal surgery for malignancy. IL-6 was measured on the first and third postoperative days (POD1, POD3), and C-reactive protein (CRP) was measured on the POD3. POC was analysed in subgroups according to Clavien‒Dindo (CD), antibiotic (ATB) treatment, intensive care unit (ICU) and hospital length of stay. The predictive power of variables for evaluated endpoints was analysed using receiver-operating characteristic (ROC) analysis and described by area under the curve (AUC). ROC analysis was adopted for the identification of optimal cut-offs. Histological analysis was performed to verify IL-6 production by the tumour.ResultsOut of 115 patients who were analysed, 42% had POC. Patients with POC had significantly higher serum levels of IL-6 on POD1 (p < 0.001) and POD3 (p < 0.001). IL-6 early on POD1 as a predictor of antibiotic treatment, ICU stay and hospital stay (AUC 0.818; 0.811; 0.771) did not significantly differ from the AUC of CRP late on POD3 (0.879; 0.838, 0.752). A cut-off IL-6 value of 113 pg/ml on POD1 and 180.5 pg/ml on POD3 in severe complications (CD > 3a) resulted in 75% and 72% sensitivity, 78.6% and 99% specificity, negative predictive value 96.4% and 97% and positive predictive value 29% and 88.9%.ConclusionThe serum level of interleukin-6 can predict severe (CD > 3a) POC early on POD1. On POD3, IL-6 is superior to CRP in terms of high positive predictive power of severe POC. Interestingly, the advantage of IL-6 on POD1 is early prediction of the need for antibiotic treatment, ICU stay and hospital stay, which is comparable to the CRP serum level late on the third POD.

Increased Expression of Inflammatory Cytokines and Discogenic Neck Pain.

Although neck pain has become a serious economic and social problem worldwide, the etiology remains poorly understood. The aim of current study is to explore the possible pathogenesis of discogenic neck pain by analyzing the relationship between inflammatory cytokines and discogenic neck pain and provide a valuable reference for the prevention and treatment of discogenic neck pain. A total of 111 cervical disc samples were collected between October 1, 2021, and October 1, 2022: 38 samples from the discogenic neck pain group, 41 samples from the symptomatic control group, and 32 samples from the normal control group. The concentration of nitric oxide (NO), interleukin (IL)-1, interleukin (IL)-6, and tumor necrosis factor alpha (TNF-α) was determined using the enzyme-linked immunosorbent assay in each sample, and the degeneration degree of the target discs were evaluated using T2-weighted sagittal magnetic resonance imaging (MRI) according to the Miyazaki disc degeneration grading system. Whether the differences among the three groups were statistically significant was tested using one-way analysis of variance and an unpaired t-test, respectively. The differences of the baseline characteristics were not statistically significant between the discogenic neck pain group and the symptomatic control group (p > 0.05). The expression of inflammatory cytokines in disc samples from the discogenic neck pain group (NO: 9.89 ± 1.75, IL-1β: 10.74 ± 1.92, IL-6:31.65 ± 2.46, and TNF-α: 5.96 ± 1.91) was increased in comparison with the disc samples from both the symptomatic control group (NO: 7.15 ± 2.78, IL-1β: 8.03 ± 1.87, IL-6: 25.79 ± 2.12, and TNF-α: 4.18 ± 2.87) and the normal control group (NO: 6.11 ± 1.37, IL-1β: 5.84 ± 2.25, IL-6: 20.65 ± 1.26, and TNF-α: 2.05 ± 0.58). The differences were statistically significant (p < 0.001). Further, there were no statistical differences in the degree of degeneration between discogenic neck pain group and symptomatic control group. The increased expression of inflammatory cytokines in diseased cervical intervertebral discs might play a key role in the pathogenesis of discogenic neck pain. Although inflammation is involved in intervertebral disc degeneration, there is no linear positive correlation between the concentration of inflammatory cytokines and the degree of disc degeneration.

Biomarkers in Endurance Exercise: Individualized Regulation and Predictive Value.

The high interindividual variability of exercise response complicates the efficient use of blood-based biomarkers in sports. To address this problem, a useful algorithm to characterize the individual regulation and predictive value of different candidate markers will be developed. Forty-nine participants completed two identical exercise trials. Blood samples were collected before, immediately after, 3 hours after, and 24 hours after completion of exercise. Plasma concentrations of interleukin (IL-) 1RA, IL-6, IL-8, IL-10, IL-15, creatine kinase (CK), cortisol, c-reactive protein (CRP), lactate dehydrogenase (LDH), and thiobarbituric acid reactive substances (TBARS) were measured. Individualized regulation was analyzed using k-means clustering and a Group Assignment Quality (GAQ) score. Regression trees with a bootstrapped-aggregated approach were used to assess the predictive qualities of the markers. For most of the markers studied, a distinction can be made between individuals who show a stronger or weaker response to a particular endurance training program. The regulation of IL-6, IL-8, IL-10, and CK exhibited a high degree of stability within the individuals. Regarding the predictive power of the markers, for all dependent variables, the most accurate predictions were obtained for cortisol and IL-8 based on the baseline value. For CK, a good prediction of recovery of maximal strength and subjective feeling of exhaustion can be made. For IL-1RA and TBARS, especially their reregulation can be predicted if the baseline level is known. Focusing individual variations in biomarker responses, our results suggest the combined use of IL-6, IL-8, IL-10, and CK for the personalized management of stress and recovery cycles following endurance exercise.

Au nanorod assembly for sensitive SERS detection of airway inflammatory factors in sputum.

In this paper, we demonstrate a surface-enhanced Raman spectroscopy (SERS) biosensor based on the self-assembly of gold nanorods (AuNRs) for the specific detection of airway inflammatory factors in diluted sputum. The AuNR surface was modified with an antibody that was able to specifically recognize an airway inflammatory factor, interleukin-5 (IL-5), so that a end-to-end self-assembly system could be obtained, resulting in an order of magnitude amplification of the Raman signal and greatly improved sensitivity. Meanwhile, the outer layer of the biosensor was coated with silicon dioxide, which improved the stability of the system and facilitated its future applications. When the detected concentration was in the range of 0.1-50pg/mL, the SERS signal generated by the sensor showed a good linear relationship with the IL-5 concentration. Moreover, it had satisfactory performance in diluted sputum and clinical subjects with asthma, which could achieve sensitive detection of the airway inflammatory factor IL-5. Overall, the developed biosensor based on the SERS effect exhibited the advantages of rapid and sensitive detecting performance, which is suitable for monitoring airway inflammatory factors in sputum.

The evaluation of oxidative stress and inflammation markers in serum and saliva of the patients with temporomandibular disorders.

Temporomandibular Disorders (TMD), as in the occurrence of many diseases, have been associated with oxidative stress (OS) resulting from the disruption of antioxidant mechanisms and the accumulation of reactive oxygen species in tissues. This study was designed to compare salivary and serum OS and inflammation markers of individuals with TMD and healthy subjects. A prospective cross-sectional study was conducted. Twenty-seven TMD patients diagnosed with disc displacement (DD) according to Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) and 17 healthy subjects were enrolled in the study. Prior to any treatment, serum, and saliva samples were taken from the patients and centrifuged, and stored at -80 °C until analyzed. All samples were examined for Interleukin-6 (IL-6), Malondialdehyde (MDA), and 8-hydroxydeoxyguanosine (8-OHdG) concentrations. There was no significant difference between the groups regarding median values of 8-OHdG, IL-6, and MDA (p > 0.05). When the relationship between serum and salivary 8-OHdG, IL-6, and MDA levels in all subjects was evaluated, there was a strong positive correlation between the levels of 8-OHdG and IL-6 in the serum (r = 0.752, p <0.001). In the study group, when the relationship between pain levels and serum and saliva 8-OHdG, IL-6, and MDA levels was assessed, a positive and strong correlation was found between the levels of 8-OHdG and IL-6 in serum. Although the strong correlation between pain scores and serum 8-OHdG and MDA levels supports the hypothesis that inflammation and OS mechanisms may be interrelated, according to the results of the study, inflammatory and OS markers in patients with TMD were not different from healthy individuals.

The Impact of 45S5-Bioactive Glass on Synovial Cells in Knee Osteoarthritis-An In Vitro Study.

Synovial inflammation in osteoarthritis (OA) is characterized by the release of cartilage-degrading enzymes and inflammatory cytokines. 45S5-bioactive glass (45S5-BG) can modulate inflammation processes; however, its influence on OA-associated inflammation has hardly been investigated. In this study, the effects of 45S5-BG on the release of cartilage-degrading metalloproteinases and cytokines from synovial membrane cells (SM) isolated from patients with knee OA was assessed in vitro. SM were cultivated as SM monocultures in the presence or absence of 45S5-BG. On day 1 (d1) and d7 (d7), the concentrations of Matrix Metalloproteinases (MMPs) and cytokines were assessed. In 45S5-BG-treated SM cultures, MMP9 concentration was significantly reduced at d1 and d7, whilst MMP13 was significantly increased at d7. Concentrations of interleukin (IL)-1B and C-C motif chemokine ligand 2 (CCL2) in 45S5-BG-treated SM cultures were significantly increased at both time points, as were interferon gamma (IFNG) and IL-6 at d7. Our data show an effect of 45S5-BG on SM activity, which was not clearly protective, anti-inflammatory, or pro-inflammatory. The influence of 45S5-BG on MMP release was more suggestive of a cartilage protective effect, but 45S5-BG also increased the release of pro-inflammatory cytokines. Further studies are needed to analyze the effect of BGs on OA inflammation, including the anti-inflammatory modification of BG compositions.

Reduced Population of CD36-/ABCA1+ Macrophages is Correlated with An Increase of Coronary Artery Disease Risk Markers in Type 2 Diabetes Mellitus

BACKGROUND: Cluster of differentiation (CD)36 and adenosine triphosphate-binding cassette transporter A1 (ABCA1) are 2 macrophages-expressed receptors that promote cholesterol uptake and efflux, in which their imbalance might be associated with the foam cell formation risk. Type 2 diabetes mellitus (T2DM) has been correlated with the increase of this plaque formation. Therefore, it is necessary to determine whether expression of CD36 and ABCA1 in macrophages are correlated with coronary artery disease (CAD) risk markers in T2DM cases.METHODS: Peripheral blood mononuclear cells (PBMC) were isolated from 13 diabetic patients and 11 healthy donors. Then, the PBMC-derived macrophages were cultured with supplement of oxidized low-density lipoprotein (ox-LDL) or lipopolysaccharide (LPS). Expression of CD36 and ABCA1 was measured using flowcytometry, meanwhile the supernatant concentration of interleukin (IL)-1b and IL-10 was measured by multiplex immunoassay.RESULTS: T2DM subjects more likely to have low proportion of CD36-ABCA+ macrophages compared to healthy donors (p=0.041) and it had negative correlation with glucose homeostasis and insulin resistance markers, including fasting blood glucose (FBG, r=-0.408, p=0.048), glycated hemoglobin (HbA1c, r=-0.380, p=0.049), triglyceride glucose index (r=-0,518, p=0.009), and high-sensitivity C-reactive protein (hs-CRP, r=-0.556, p=0.005). Moreover, it also had a negative correlation with atherogenic markers such as triglyceride (r=-0.417, p=0.043), triglyceride/HDL, and LDL/HDL, but had positive correlation with HDL (r=0.540, p=0.007). Most of T2DM subjects had high IL-1β/IL-10 ratio after ox-LDL and LPS stimulation (p=0.02 and p=0.05, respectively).CONCLUSION: Reduced proportion of CD36-ABCA1+ macrophages followed with high IL-1β/IL-10 can be a marker of CAD in T2DM.KEYWORDS: type 2 diabetes mellitus, coronary artery disease, macrophages, ABCA1, CD36

Inflammatory endotypes of adenoidal hypertrophy based on a cluster analysis of biomarkers

ObjectiveTo identify adenoid inflammatory endotypes based on inflammatory markers, match endotypes to phenotypes, and predict endotypes. MethodsThis cross-sectional study included 72 children with adenoid hypertrophy. Thirteen inflammatory markers and total immunoglobulin E (TIgE) in adenoid tissue were analyzed using Luminex and enzyme-linked immunosorbent assay (ELISA) for performing cluster analysis. Correlation analysis was used to examine the characteristics of each cluster. Receiver operating characteristic (ROC) curve analysis was performed to screen for preoperative characteristic data with predictive value for adenoid inflammation endotype. ResultsThe patients were divided into four clusters. Cluster 1 exhibited non-type 2 signatures with low inflammatory marker concentrations, except for the highest expression of Th1-related cytokines. Cluster 2 showed a non-type 2 endotype with the highest concentration of interleukin (IL)-17A and IL-22. Cluster 3 exhibited moderate type 2 inflammation, with the highest concentration of neutrophil factors. Cluster 4 demonstrated significant type 2 inflammation and moderate neutrophil levels. The proportions of AR and serum TIgE levels increased from clusters 1 to 4, and there was a gradual increase in the prevalence of chronic sinusitis from low to high neutrophilic inflammation. The area under the ROC curve for serum TIgE was higher than those for combined or other separate preoperative characteristics for predicting non-type 2 and type 2 inflammation in the adenoid tissue. ConclusionsThe evaluation of cytokines in adenoid tissue revealed four endotypes. Serum TIgE level was an important indicator of the endotype of adenoid inflammation. Identification of adenoid inflammatory endotypes can facilitate targeted treatment decisions.

In search of biomarkers for low back pain: can traction therapy effectiveness be prognosed by surface electromyography or blood parameters?

Background: Lumbar traction therapy is a common method to reduce low back pain (LBP) but is not always effective. The search for biomarkers that would prognose the effectiveness of LBP management is one priority for improving patients' quality of life. Objectives: 1) To determine the phenotype of patients benefiting most from lumbar traction therapy. 2) To correlate systemic and electromyographic biomarkers with pain and pain-related disability. Methods: Data on muscle bioelectrical activity (surface electromyography [SEMG]) in the flexion-extension task, the concentrations of twelve systemic biochemical factors, LBP intensity (Visual Analog Scale), the Oswestry Disability Index, and the Roland-Morris Disability Questionnaire (RMDQ) were collected before and 72h after 20 sessions of lumbar traction therapy. Patients were divided into responders and nonresponders based on the criterion of a 50% reduction in maximal pain. Results: The responders had lower maximal muscle bioactivity in the extension phase on the left side (p < 0.01) and higher flexion-extension ratios on both sides of the body in the SEMG (left: p < 0.05; right: p < 0.01), and higher adipsin, interleukin-2, interleukin-4, and interleukin-10 concentrations (p < 0.05) than nonresponders. Patients with higher interleukin-4 concentrations before therapy achieved greater reductions in maximal pain in the sitting position, bioelectrical muscle activity in flexion, and flexion-relaxation ratio on the left side of the body. Changes in adipsin and interleukin-4 concentrations correlated with changes in LBP intensity (r = 0.68; r = -0.77). Changes in stem cell growth factor and interleukin-17A correlated with changes in RMDQ (R = 0.53) and bioelectrical muscle activity in extension (left: R = -0.67; right: R = -0.76), respectively. Conclusion: Responders to traction therapy had SEMG indices of less favorable muscle activity in the flexion-extension task and elevated indices of inflammation before the study. For the first time, interleukin-4 was indicated as a potential biomarker for prognosing post-therapy changes in pain intensity and muscle activity.

Probiotic-Fermented Distillers Grain Alters the Rumen Microbiome, Metabolome, and Enzyme Activity, Enhancing the Immune Status of Finishing Cattle.

A total of 30 Simmental crossbred cattle (6.50 months old, 265.0 ± 22.48 kg) were randomly divided into three groups, with 10 heads per group, and fed for 45 days. The diet treatments consisted of the Control group without PFDG supplementation, the PFDG-15% group with 15% PFDG substituting for 15% concentrate, and PFDG-30% group with 30% PFDG substituting for 30% concentrate. The results showed that compared with the Control group, the average daily gain (ADG) of the cattle in the PFDG-30% group decreased significantly (0.890 vs. 0.768 kg/d, p = 0.005). The serum malondialdehyde content of cattle in the PFDG-15% and PFDG-30% groups decreased significantly (p = 0.047) compared to that of the Control group. However, the serum superoxide dismutase activity of cattle in the PFDG-30% group was significantly higher than that of the Control group (p = 0.047). Meanwhile, both the PFDG-15% and PFDG-30% groups (1758.47 vs. 2061.30 μg/mL) showed higher serum levels of immunoglobulin G, while the interleukin-10 concentration was lower in the PFDG-30% group (p = 0.027). In addition, the PFDG-15% and PFDG-30% groups shifted the rumen microbiota by improving the abundances of F082 (related to propionic acid production) and fiber-degrading bacteria (Lachnospiraceae_UGG-009 and Prevotellaceae_UCG-001) and reducing the abundance of the disease-associated bacteria Selenomonas. A Kyoto encyclopedia of genes and genomes (KEGG) analysis illustrated that three key metabolic pathways, including phenylalanine metabolism, pyrimidine metabolism, and tryptophan metabolism, were enriched in the PFDG-15% group, but eight key metabolic pathways, including arachidonic acid metabolism, were enriched in the PFDG-30% group. Importantly, both the PFDG-15% and PFDG-30% groups increased (p < 0.01) the activities of cellulase, lipase, and protease in the rumen. Finally, the different bacterial abundance in the rumen was associated with changes in the ADG, serum antioxidant capacity, immune status, rumen enzyme activity, and metabolites. These results suggest that PFDG alters rumen microbiome abundance, metabolome, and enzyme activity for enhancing serum antioxidant capacity and the immune status, but when the supplemental level reaches 30%, it has a negative effect on ADG and the anti-inflammatory factors in finishing cattle.

Effects of proprotein convertase subtilisin-kexin type 9 inhibitors on inflammatory and hemostatic parameters in post myocardial infarction patients

Despite progress in treatment, elevated levels of low-density lipoprotein cholesterol (LDL-C) and lipoprotein (a) (Lp(a)), represent a significant part of the residual risk. Both are associated with inflammation and the coagulation fibrinolytic system. The purpose of our research was to evaluate the effect of proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) on lipid parameters and indicators of inflammation, coagulation and fibrinolysis. We included 100 post myocardial infarction (MI) patients with insufficiently controlled LDL-C values despite the maximum dose of statin, and highly elevated Lp(a). Patients received alirocumab or evolocumab (150 mg sc or 140 mg sc every two weeks, respectively), or placebo for 6 months.In patients receiving PCSK9i, a significant decrease in total cholesterol (TC), LDL-C, triglycerides (TG) and Lp(a), and an increase in high density lipoprotein cholesterol (p < 0.001 for all) was found. Before treatment, the concentrations of TC, LDL-C and TG correlated with the concentrations of thrombin activatable fibrinolysis inhibitor (r = 0.41, p < 0.001; r = 0.353, p < 0.001; r = 0.311, p = 0.003, respectively), and plasminogen activator inhibitor-1 (r = 0.302, p = 0.007; r = 0.218, p = 0.049; r = 0.278; p = 0.013, respectively). The concentrations of TC and LDL-C correlated with overall fibrinolytic potential (r = −0.220, p = 0.034; r = −0.207, p = 0.047, respectively). The concentration of TG was related to the concentration of interleukin 6 (r = 0.290, p = 0.004) and interleukin 8 (r = 0.332, p = 0.001). No correlations between Lp(a) and inflammatory or hemostatic variables were found. No associations were found after treatment. Our results show that inflammatory cytokines and fibrinolytic parameters are related to LDL-C and not Lp(a) in post-MI patients before and with neither of them following PCSK9i treatment.The trial registration number: NCT04613167, Date of registration: November 3, 2020.

Evaluation of the relationship of cytokines concentrations tumor necrosis factor-alpha, interleukin-6, and C-reactive protein in obese diabetics and obese non-diabetics: A comparative study.

Obesity has been linked to a low-grade inflammatory process in the white adipose tissue. Our study aims to detect the relationship between cytokine levels of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and C-reactive protein (CRP) in obese diabetics, compared to obese non-diabetics, Iraqi individuals. Ninety Iraqi adults, 45 type 2 diabetic and 45 non-diabetic obese, were selected as controls. Serum levels of TNF-α, IL-6, CRP, homeostatic model assessment for homeostasis model assessment of insulin resistance (HOMA-IR), body fat, and body mass index (BMI) were measured. The concentration of TNF-α, IL-6, and CRP were significantly greater in the obese diabetics, compared to the obese non-diabetics. BMI was significantly positively correlated with the concentration of TNF-α, IL-6, and CRP in the two groups. At the same time, HOMA-IR was non-significantly positively associated with them in obese diabetics. In contrast, the correlation was significantly positive between HOMA-IR with TNF-a, IL-6, and CRP in the obese non-diabetics group. Obese diabetics have more inflammation than obese non-diabetics as evidenced by the former's higher levels of TNF-α and IL-6. Obesity-related imbalances disrupt metabolic processes and increase CRP, TNF-, and IL-6 levels. Therefore, IR is promoted by the increase of cytokines.

Periodic dynamic observation and analysis of cellular and humoral immunity indexes of adults infected with Omicron BA.1

Objective: To analyze the immunological characteristics and antibody changes of patients infected with the Omicron BA.1 and evaluate the possibility of secondary infection. Methods: A total of 104 patients infected with Omicron BA.1 in the Jinnan District of Tianjin from January 8 to February 2, 2022, were included in the study. The control group and case group were matched 1∶1 based on age, sex and vaccination status. Serum was collected from the case group and control group at 3, 6 and 9 months after infection. The serum levels of interleukin4 (IL-4), IL-5 and interferon-gamma (IFN-γ), as well as the positive rates of IgG, IgG1 and IgG2, were detected by ELISA. Results: The highest concentration of IFN-γ in the case group at 6 months after infection was 145.4 pg/ml, followed by a decrease in concentration. The concentrations of IL-4 and IL-5 began to decrease at 6 months after infection (all P<0.001). There was no significant difference in the IgG2 positive rate between the case group and the control group at 6 months after BA.1 infection. However, at 9 months, there was a significant decrease compared to the control group (P=0.003). The ratio of IFN-γ/IL4 at 3 months after infection in the case group was lower than that in the control group (P<0.001). There was no significant difference in the ratio between the case group and the control group at 9 months after infection. Conclusion: The cellular immune function has been impaired at 3 months after infection with BA.1, and the specific cellular immune and humoral immune functions decrease significantly after 6 months, and the risk of secondary infection increases.

Metabolic Blood Hormones in Young People With Electrocardiographic Signs of Ischemic Myocardial Changes

Aim To study changes in blood concentrations of metabolic hormones and adipocytokines in people aged 25-44 years with electrocardiographic (ECG) signs of ischemic changes in the myocardium.Material and methods This study was a part of a cross-sectional survey of a random sample of Novosibirsk population aged 25-44 years. The study included 1363 people divided into two groups: group 1, subjects with ECG signs of ischemic changes in the myocardium and group 2, subjects without ECG changes. Blood serum concentrations of adipocytokines and metabolic hormones were measured by multiplex assay on a Luminex MAGPIX flow-through fluorometer.Results The group with ECG signs of myocardial ischemia had higher blood concentrations of adiponectin, resistin, glucagon, and interleukin 6 (IL-6) than in the comparison group. A multivariate logistic regression analysis showed that the glucagon concentration was associated with the presence of ECG signs of myocardial ischemia (OR, 1.019; CI, 1.018-1.034; p=0.017).Conclusion In young people aged 25-44 years, higher blood concentrations of glucagon are associated with the presence of ECG signs of myocardial ischemia.

Assessment of CYP3A-mediated drug interaction via cytokine (IL-6) elevation for mosunetuzumab using physiologically-based pharmacokinetic modeling.

Mosunetuzumab is a CD3/CD20 bispecific antibody. As an on-target effect, transient elevation of interleukin-6 (IL-6) occurs in early treatment cycles. A physiologically-based pharmacokinetic (PBPK) model was developed to assess potential drug interaction caused by IL-6 enzyme suppression on cytochrome P450 3A (CYP3A) during mosunetuzumab treatment. The model's performance in predicting IL-6 CYP3A suppression and subsequent drug-drug interactions (DDIs) was verified using existing clinical data of DDIs caused by chronic and transient IL-6 elevation. Sensitivity analyses were performed for a complete DDI risk assessment. The IL-6 concentration- and time-dependent CYP3A suppression during mosunetuzumab treatment was simulated using PBPK model with incorporation of invitro IL-6 inhibition data. At clinically approved doses/regimens, the DDI at maximum CYP3A suppression was predicted to be a midazolam maximum drug concentration in plasma (Cmax ) and area under the plasma drug concentration-time curve (AUC) ratio of 1.17 and 1.37, respectively. At the 95th percentile of IL-6 concentration level or when gut CYP3A suppression was considered, the predicted DDI risk for mosunetuzumab remained low (<2-fold). The PBPK-based DDI predictions informed the mosunetuzumab product label to monitor, in early cycles, the concentrations and toxicities for sensitive CYP3A substrates with narrow therapeutic windows.

Acute inflammation elicits decreased blood pressure but similar arterial stiffness in young African American adults.

African Americans (AA) have a higher risk for cardiovascular disease (CVD) as compared to their White (W) counterparts. CVD is characterized by increased blood pressure (BP), arterial stiffness and systemic inflammation. An acute inflammatory stimulus may explain physiological manifestations responsible for amplified CVD in AA that are not apparent at rest. The purpose of this study was to evaluate central and peripheral BP, central and local arterial stiffness, and indices of pulse wave morphology in young healthy AA and W participants in response to acute inflammation. Concentrations of the inflammatory cytokine interleukin-6 (IL-6) and measures of central and peripheral BP, central arterial stiffness (carotid-femoral pulse wave velocity (cfPWV)), local carotid arterial stiffness (β-stiffness, elastic modulus (Ep)), and indices of pulse wave morphology were assessed in 28 participants (21±2years, AA: n = 11) at baseline (BL), 24h and 48h post-inflammation. Changes in IL-6 concentrations (ΔIL-6) were significantly greater at 24h as compared to 48h post-inflammation (0.652±0.644 vs. -0.146±0.532pg/μl, P≤0.0001). Among AA participants, central and peripheral diastolic BP were significantly decreased at 24h post-inflammation as compared to BL (aortic diastolic BP: -4±4mmHg, P=0.016; brachial diastolic BP: -4±4mmHg, P=0.014). AA participants also experienced a significant decrease in central and peripheral mean arterial BP at 48h post-inflammation as compared to BL (aortic mean arterial pressure: -4±4mmHg, P=0.009; brachial mean arterial pressure: -4±4mmHg, P=0.012). Despite haemodynamic changes, there were no differences in central or local carotid arterial stiffness or indices of pulse wave morphology.