Interleukin-6 Concentrations Research Articles

Sinensetin inhibits the movement ability and tumor immune microenvironment of non-small cell lung cancer through the inactivation of AKT/β-catenin axis.

Although current treatment strategies have improved clinical outcomes of non-small cell lung cancer (NSCLC) patients, side effect and prognosis remain a hindrance. Thus, safer and more effective therapeutical drugs are needed for NSCLC. Sinensetin (Sin) is a flavonoid from citrus fruits, which exhibits antitumor effect on diverse cancers. However, the effect and mechanism of Sin on NSCLC remain unknown. In this study, NSCLC cell lines, and tumor-bearing mice were treated with Sin. The effect and mechanism of Sin were addressed using cell counting kit-8, transwell, enzyme-linked immunosorbent assay, hematoxylin and eosin, immunohistochemistry, and western blot analysis assays in both cell and animal models. Sin reduced the cell viability of A549 and H1299, with the IC50 of 81.46 µM and 93.15 µM, respectively. Sin decreased invaded cell numbers, the expression of N-cadherin and vascular endothelial growth factor A (VEGFA), while increased the E-cadherin level, the cytotoxicity of CD8+ T cells, and the concentration of interferon-γ (IFN-γ), interleukin-2 (IL-2), and tumor necrosis factor-α (TNF-α) in NSCLC cells. Mechanistically, Sin declined the expression of protein kinase B (AKT)/β-catenin pathway, which was restored with the application of SC79, an activator of AKT. The inhibitory role of Sin in NSCLC cell proliferation, invasion, epithelial-mesenchymal transition (EMT) and immune escape was reversed by the management of SC79. In vivo, Sin reduced tumor size and weight, and the expression of N-cadherin, VEGFA, and AKT/β-catenin pathway, but enhanced the level of E-cadherin and IFN-γ. Taken together, Sin suppressed cell growth, invasion, EMT and immune escape via AKT/β-catenin pathway in NSCLC.

The Role of Interleukin-8 in the Estimation of Responsiveness to Steps 1 and 2 of Periodontal Therapy.

To investigate the association between interleukin-8 (IL-8) levels in gingival crevicular fluid (GCF) and total oral fluid (TOF) and the responsiveness to steps 1 and 2 of periodontal therapy. One-hundred and fifty-nine patients affected by periodontitis received steps 1 and 2 of periodontal therapy. At baseline, TOF and GCF samples were collected and analysed for IL-8 (Il-8TOF/IL-8GCF) using flow cytometry. Therapy outcomes were relative proportions of residual periodontal pockets (PPD%), pocket closure (PC) rates and pocket probing depth (PPD) reductions; these were associated with IL-8TOF/IL-8GCF. High IL-8TOF was significantly associated with higher residual PPD% (p = 0.044) and lower PPD reduction compared to low IL-8TOF (high 0.79 ± 1.20 mm vs. low 1.20 ± 1.20 mm, p < 0.001) in non-smokers, while in smokers high IL-8GCF was related to lower PPD reduction (high 0.62 ± 1.22 mm vs. low 0.84 ± 1.12 mm, p = 0.009). Furthermore, high baseline IL-8TOF was significantly associated with poorer PC rates compared to medium and low concentrations in both non-smokers (high 41% vs. medium 55% vs. low 58%, p < 0.001) and smokers (high 34% vs. medium 44% vs. low 46%, p < 0.001). High IL-8 concentrations at baseline had a significant impact on residual PPD%, PC rates and PPD reduction. The findings suggest that, especially in non-smokers, baseline IL-8 levels collected from the TOF could serve as a component in the estimation of responsiveness to steps 1 and 2 of periodontal therapy.

Interleukin 6 in asymptomatic patients with nonsevere aortic valve stenosis: a post-hoc study of the SEAS trial

Abstract Background Inflammation plays a pivotal role in the pathogenesis of aortic valve stenosis (AS) through cytokine-mediated valve calcification. Studies of explanted valves found associations of an elevated pro-inflammatory cytokine, Interleukin 6 (IL-6), with increased postoperative mortality. However, limited knowledge exists regarding the prognostic value of elevated circulating IL-6 in asymptomatic patients with nonsevere AS. Purpose To investigate the hypothesis that elevated plasma IL-6 concentration ≥7 pg/mL (above the upper limit of normal 95th percentile) correlates with more severe AS and a higher risk of adverse outcomes in asymptomatic patients with nonsevere AS. Methods We analyzed data of 1574 asymptomatic patients who had mild-to-moderate AS, preserved systolic and kidney function, no overt cardiovascular diseases, and an event-free follow-up one year after enrollment in the randomized Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) trial. We ascertained the correlation of year-0 and year-1 IL-6 levels with echocardiographic AS severity, defined as moderate-severe AS in the presence of ≥2 measurements at year-0: aortic valve area &amp;lt;1 cm², mean pressure gradient ≥40 mmHg, maximal transaortic velocity ≥4 m/s, and velocity ratio &amp;lt;0.25. Multivariable regression examined correlations between IL-6 at year-0 and clinical variables. Cox proportional hazard models and competing risk analyses examined associations of elevated IL-6 at year-1 and 4-year risk of the primary composite endpoint of major cardiovascular events (MACE) comprising the first event of cardiovascular death, aortic valve replacement, hospitalization with heart failure, myocardial infarction, percutaneous coronary intervention, coronary artery bypass graft, or ischemic stroke. Results At year-0, among 1574 patients with a mean (SD) age of 67.5 (9.7) years, 629 (40.0%) were women, 263 (16.7%) had moderate-severe AS, and 194 (12.3%) had elevated IL-6. The median relative IL-6 change from year-0 to year-1 was 1.0 (IQR, 0.8-1.4) across AS-severity groups (P=0.12) (Figure 1). In adjusted models, IL-6 at year-0 did not correlate with AS-severity (P=0.30). In mild AS, an elevated IL-6 at year-1 was associated with an increased 4-year MACE risk (HR 1.40; 95% CI, 1.02-1.92; p=0.04) in adjusted Cox regression analyses (Figure 2A). In sensitivity analyses, the annual IL-6 increase &amp;gt;50% combined with normal IL-6 was associated with an increased 4-year MACE-risk of HR 1.48 (95% CI, 1.10-2.00; P=0.009) in patients with mild AS and 1.82 (95% CI, 0.68-1.74; P=0.73) in patients with moderate-severe AS (all P for interaction&amp;gt;0.25) (Figure 2C-D). Conclusion In asymptomatic patients with nonsevere AS, circulating IL-6 remains stable within the reference range in 7 out of 8 patients during a 1-year follow-up, regardless of AS severity. An elevated IL-6 was associated with a 1.4-fold increased 4-year MACE-risk in patients with mild AS, suggesting its possible role as an early risk marker.Figure 1Figure 2

Effect of Electrical Stimulation of the Vagus Nerve on Inflammation in Rats With Spinal Cord Injury

ObjectiveThe purpose of this study was to assess the effect of electroacupuncture stimulation (EAS) of the vagus nerve on the inflammatory response in rat models of spinal cord injury (SCI). MethodsThe T10 SCI model in adult male Sprague Dawley rats was established using the modified Allen's method. The EAS group was treated with the therapy on the vagus nerve of rat ear nails, while the SCI group did not receive any EAS treatment. The degree of inflammatory infiltration was reflected by hematoxylin-eosin staining. The inflammatory cytokines in spinal cord tissues, cerebrospinal fluid inflammation, and peripheral blood were detected by enzyme-linked immunosorbent assay. Changes in astrocytes and microglia were assessed using an immunofluorescence assay. ResultsElectroacupuncture stimulation treatment inhibited inflammatory infiltration, as well as the concentrations of interleukin-6, interleukin-1β, tumor necrosis factor-α, astrocytes, and microglia at 1, 6, and 24 hours after 1 EAS treatment. Multiple EAS treatments had an obvious effect on SCI inflammation. ConclusionA single EAS treatment had a limited effect on inflammation, but multiple treatments had a significant inhibitory effect on inflammation.

Inflammatory Cytokines and Cognition in Alzheimer's Disease and Its Prodrome.

The aim of this study was to investigate the association between blood levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) and cognitive impairments among elderly individuals. Peripheral concentration of TNF-α and IL-6 were measured in all subjects. To assess individual cognitive function, the Consortium to Establish a Registry for Alzheimer's Disease Neuropsychological Assessment Battery (CERAD-NP) was used, and standardized scores (z-scores) were calculated for each test. Cytokine levels were compared between the diagnostic groups, and correlations between blood inflammatory factor levels and z-scores were analyzed. The 37 participants included 8 patients with Alzheimer's disease (AD), 15 subjects with mild cognitive impairment (MCI), and 14 cognitively healthy controls. TNF-α and IL-6 levels were higher in patients with AD than in healthy controls. TNF-α levels were higher in the AD group than in the MCI group. However, after adjusting for age, the associations between diagnosis and TNF-α and IL-6 were not significant. The higher the plasma IL-6 level, the lower the z-scores on the Boston Naming Test, Word List Learning, Word List Recognition, and Constructional Recall. The higher the serum TNF-α level, the lower the z-scores on the Word List Learning and Constructional Recall. Negative correlation between serum TNF-α level and the z-score on Word List Learning remained significant when age was adjusted. The difference in the blood levels of TNF-α and IL-6 between the diagnostic groups may be associated with aging. However, elevated TNF-α levels were associated with worse immediate memory performance, even after adjusting for age.

Immune Effect of Co-Culture of Dendritic Cells and Cytokine-Induced Killer Cells on Prostate Cancer Cells.

It was to explore the immune outcome of co-culture of dendritic cells (DC) and cytokine-induced killer cells (CIK) on prostate cancer (PCa) cells. Peripheral blood mononuclear cells (PBMCs) were extracted from healthy blood donors. DC and CIK cells were induced and co-cultured. The proliferation and phenotypic changes of DC, CIK, and DC-CIK cells/groups were observed. Model rats were constructed by injecting PC3 PCa cells into the abdominal cavity. The successful 50 cases were divided into a negative control group, a chemotherapy group, a DC group, a CIK group, and a DC-CIK treatment group (each consisting of 10 rats) to observe tumor progression. The secreted concentrations of interleukin-12 (IL-12) ((103.67 ± 2.77) pg/mL) and interferon-γ (IFN-γ) ((730.09 ± 23.52) pg/mL) were higher in DC-CIK group as against DC and CIK groups; the proliferation of CIK was higher in DC-CIK group as against CIK within 12 to 20 days of culture. The positive rate (PR) of CD3+/ CD56+ and CD8+ was higher and that of CD45RA+ was lower in DC-CIK group as against CIK.The killing rate of the DC-CIK group was higher than that of the DC and CIK groups at a target effect ratio of 10:1/20:1/50:1 (P < 0.05). After the treatment, the body weight of rats in the chemotherapy group, DC group, and CIK group was significantly reduced (P < 0.05), while no significant changes were observed in the negative control group and DC-CIK group (P > 0.05). After 25 days of treatment, the tumor size in the DC-CIK group was significantly smaller compared to the negative control group, chemotherapy group, DC group, and CIK group; the necrotic area of the tumor tissue in the DC-CIK group was also significantly larger than that in the negative control group, chemotherapy group, DC group, and CIK group (P < 0.05). Co-culture of DC and CIK is excellent in enhancing the proliferation of CIK cells, increasing the secretion of IL-12 and IFN-γ, and enhancing the activity of immune cells and anti-tumor ability, showing its potential in anti-PCa tumor immunotherapy.

T-Cell Phenotypes and Systemic Cytokine Profiles of People Living with HIV Admitted to Hospital with COVID-19

Whether SARS-CoV-2 infection leads to a higher mortality and morbidity in people living with HIV (PLWH) in Africa remains inconclusive. In this study, we explored the differences in the T-cell phenotypes between people with and without HIV on the day of admission (V1) and ±7 days later (V2), as well as their cytokine/chemokine profiles on V1. Patients admitted with COVID-19 were recruited between May 2020 and December 2021 from the Steve Biko Academic and Tshwane District Hospitals in Pretoria, South Africa. Of 174 patients, 37 (21%) were PLWH. T-cell profiles were determined by flow cytometry, and cytokine levels were determined using a multiplex suspension bead array. PLWH were significantly younger than those without HIV, and were more likely to be female. In an adjusted analysis, PLWH had higher percentages of CD4+ central memory (CM) programmed cell death protein 1 (PD-1)+, CD8+ effector memory (EM)2, and CD8+ EM4 CD57+ cells, as well as higher concentrations of interleukin (IL)-35 at admission. PLWH with CD4+ T-cell counts of &gt;200 cells/mm3 had altered CD4+ and CD8+ T-cell profiles, lower levels of systemic inflammation measured by plasma ferritin and PCT levels, and less severe disease. PLWH with CD4+ T-cell counts of &lt;200 cells/mm3 on admission had higher concentrations of IL-6 and lower levels of IL-29. At V2, the percentages of CD4+ CM PD-1+ T-cells and CD8+ EM4 T-cells co-expressing CD57 and PD-1 remained higher in PLWH, while all other CD8+ EM populations were lower. Fewer CD8+ EM T-cells after ±7 days of admission may be indicative of mechanisms inhibiting EM T-cell survival, as indicated by the higher expression of IL-35 and the T-cell maturation arrest observed in PLWH. This profile was not observed in PLWH with severe immunodeficiency, highlighting the need for differentiated care in the broader PLWH population.

The predictive capacity of biomarkers for clinical pulmonary oedema in patients with severe falciparum malaria is low: a prospective observational study

BackgroundPulmonary oedema is a feared and difficult to predict complication of severe malaria that can emerge after start of antimalarial treatment. Proinflammatory mediators are thought to play a central role in its pathogenesis.MethodsAn exploratory study was conducted to evaluate the predictive capacity of biomarkers for development of clinical pulmonary oedema in patients with severe falciparum malaria at two hospitals in Bangladesh. Plasma concentrations of interleukin-6 (IL-6), IL-8, tumour necrosis factor (TNF), soluble Receptor of Advanced Glycation End-products (sRAGE), surfactant protein-D (SP-D), club cell secretory protein (CC16), and Krebs von den Lungen-6 (KL-6) on admission were compared with healthy controls. Correlations between these biomarker and plasma lactate and Plasmodium falciparum histidine-rich protein 2 (PfHRP2) levels were evaluated. Receiver Operating Characteristic (ROC) curves were constructed to assess the predictive capacity for clinical pulmonary oedema of the biomarkers of interest.ResultsOf 106 screened patients with falciparum malaria, 56 were classified as having severe malaria with a mortality rate of 29%. Nine (16%) patients developed clinical pulmonary oedema after admission. Plasma levels of the biomarkers of interest were higher in patients compared to healthy controls. IL-6, IL-8, TNF, sRAGE, and CC16 levels correlated well with plasma PfHRP2 levels (rs = 0.39; P = 0.004, rs = 0.43; P = 0.001, rs = 0.54; P < 0.001, rs = 0.44; P < 0.001, rs = 0.43; P = 0.001, respectively). Furthermore, IL-6 and IL-8 levels correlated well with plasma lactate levels (rs = 0.37; P = 0.005, rs = 0.47; P < 0.001, respectively). None of the biomarkers of interest had predictive capacity for development of clinical pulmonary oedema.ConclusionsIL-6, IL-8, TNF, sRAGE, SP-D, CC16 and KL-6 cannot be used in predicting clinical pulmonary oedema in severe malaria patients.

Impact of Long-Term Atorvastatin Therapy on the Development of Chronic Lung Allograft Dysfunction in Patients with Azithromycin Prophylaxis after Lung Transplantation

ObjectiveTo assess the impact of long-term atorvastatin (ATO) therapy on reducing recipient inflammation and immune response, thus lowering the risk of chronic lung allograft dysfunction (CLAD) in lung transplant recipients. This study aimed to investigate the effects of ATO on overall survival, lung function recovery, and its influence on inflammatory factors alongside azithromycin (AZI) prophylaxis. MethodsThis retrospective single-center study included lung transplant recipients from January 2017 to December 2022. Patients who survival >1 year after lung transplantation and who were receiving AZI prophylaxis for >6 months were selected. Outcome measures involved pulmonary function assessments at various time points after AZI treatment, complete blood cell analysis, and inflammatory factor evaluations. ResultsThe incidence of CLAD was significantly lower in the long-term ATO group compared with those not on ATO (P = .011). Long-term ATO treatment significantly delayed CLAD onset after lung transplantation (850 days vs. 630 days; P = .041), with patients showing notably enhanced lung function recovery within 6 months of AZI therapy compared with the non-ATO group. Neutrophil levels decreased in patients with CLAD, and interleukin-6 concentrations significantly decreased in the AZI + ATO group compared with the AZI group. Overall patient survival was significantly better in the AZI+ATO group than in the AZI group (P = .02). ConclusionIn cases where CLAD develops despite AZI prophylaxis, long-term ATO treatment may lead to short-term improvements in lung function. It could also decrease inflammation levels in lung transplant recipients and enhance overall survival. The combination of AZI and long-term ATO therapy may be beneficial for CLAD prevention.

Assessing the Usefulness of Interleukin-8 as a Biomarker of Inflammation and Metabolic Dysregulation in Dairy Cows.

The study aimed to evaluate interleukin-8 (IL-8) as a biomarker for udder inflammation in dairy cows and to explore its associations with various metabolic parameters indicative of systemic inflammation and metabolic dysregulation. Dairy cows (multiparous) were categorized into five somatic cell count (SCC) classes: Class I (<100,000 cells/mL; n = 45), Class II (100,000-200,000 cells/mL; n = 62), Class III (201,000-400,000 cells/mL; n = 52), Class IV (401,000-1,000,000 cells/mL; n = 73), and Class V (>1,000,000 cells/mL; n = 56). The study quantified IL-8 levels and analyzed their correlations with NEFAs (non-esterified fatty acids), BHBA (beta-hydroxybutyrate), GGTP (gamma-glutamyltransferase), and AspAT (aspartate aminotransferase). IL-8 concentrations demonstrated a significant and progressive increase across the SCC classes, establishing a strong positive correlation with SCC (p < 0.01). Additionally, IL-8 levels exhibited positive correlations with GGTP (p < 0.01) and AspAT (p < 0.01), indicating that elevated IL-8 is associated with increased hepatic enzyme activities and potential liver dysfunction. Furthermore, IL-8 showed significant positive correlations with NEFAs (p < 0.01) and BHBA (p < 0.05), linking higher IL-8 levels to metabolic disturbances such as ketosis and negative energy balance. Variations in metabolic parameters, including NEFAs, BHBA, GGTP, and AspAT, across the SCC classes underscored the association between elevated SCC levels and metabolic dysregulation in dairy cows. These findings highlight the interrelated nature of the inflammatory responses and metabolic disturbances in dairy cattle, emphasizing that an elevated SCC not only signifies udder inflammation but also correlates with systemic metabolic alterations indicative of ketosis and liver damage.

Uncovering the interleukin-12 pharmacokinetic desensitization mechanism and its consequences with mathematical modeling.

The cytokine interleukin-12 (IL-12) is a potential immunotherapy because of its ability to induce a Th1 immune response. However, success in the clinic has been limited due to a phenomenon called IL-12 desensitization - the trend where repeated exposure to IL-12 leads to reduced IL-12 concentrations (pharmacokinetics) and biological effects (pharmacodynamics). Here, we investigated IL-12 pharmacokinetic desensitization via a modeling approach to (i) validate proposed mechanisms in literature and (ii) develop a mathematical model capable of predicting IL-12 pharmacokinetic desensitization. Two potential causes of IL-12 pharmacokinetic desensitization were identified: increased clearance or reduced bioavailability of IL-12 following repeated doses. Increased IL-12 clearance was previously proposed to occur due to the upregulation of IL-12 receptor on T cells that causes increased receptor-mediated clearance in the serum. However, our model with this mechanism, the accelerated-clearance model, failed to capture trends in clinical trial data. Alternatively, our novel reduced-bioavailability model assumed that upregulation of IL-12 receptor on T cells in the lymphatic system leads to IL-12 sequestration, inhibiting the transport to the blood. This model accurately fits IL-12 pharmacokinetic data from three clinical trials, supporting its biological relevance. Using this model, we analyzed the model parameter space to illustrate that IL-12 desensitization occurs over a robust range of parameter values and to identify the conditions required for desensitization. We next simulated local, continuous IL-12 delivery and identified several methods to mitigate systemic IL-12 exposure. Ultimately, our results provide quantitative validation of our proposed mechanism and allow for accurate prediction of IL-12 pharmacokinetics over repeated doses.

The Prospect of Improving Pancreatic Cancer Diagnostic Capabilities by Implementing Blood Biomarkers: A Study of Evaluating Properties of a Single IL-8 and in Conjunction with CA19-9, CEA, and CEACAM6.

Background/Objectives: This study aims to evaluate the possible clinical application of interleukin 8 (IL-8) as a single biomarker and its capabilities in combination with carbohydrate antigen (CA19-9), carcinoembryonic antigen (CEA), and carcinoembryonic antigen cell adhesion molecule 6 (CEACAM6) as diagnostic and prognostic tools for pancreatic ductal adenocarcinoma (PDAC). Methods: A total of 170 serum samples from patients with PDAC (n = 100), chronic pancreatitis (CP) (n = 39), and healthy individuals (n = 31) were analysed. IL-8 and CEACAM6 were measured by an enzyme-linked immunosorbent assay (ELISA). CA19-9 and CEA were determined by chemiluminescent microparticle immunoassay, and bilirubin was quantified using a diazonium salt reaction. Receiver operating characteristic curve analysis, logistic regression, and Kaplan-Meier analyses were performed to evaluate the properties of a single IL-8 and in combination with other biomarkers. Results: The concentrations of IL-8 were statistically significantly higher in the PDAC group compared to the CP and control groups. Heterogeneous levels of IL-8 correlated with PDAC stages (p = 0.007). IL-8 had good and satisfactory diagnostic efficacy in differentiating PDAC from controls (0.858; p < 0.001) and patients with CP (0.696; p < 0.001), respectively. High and low expressions of IL-8 were not significantly associated with overall survival (OS) or disease-free survival (DFS). A combination of IL-8, CEACAM6, and CA19-9 reached the highest AUC values for differentiating PDAC from the control group. The best classification score between PDAC and the control group with CP patients was obtained by merging IL-8 and CA19-9 (0.894; p < 0.001). Conclusions: These results provide compelling evidence of IL-8 as a promising diagnostic biomarker. Nonetheless, due to the high complexity of PDAC, only the conjunction of IL-8, CA19-9, and CEACAM6 integrates sufficient diagnostic capabilities.

Microfluidic-SERS sensing system based on dual signal amplification and aptamer for gastric cancer detection.

Studies have found that matrix metalloproteinase-9 (MMP-9) and interleukin-6 (IL-6) play an important role in tumorigenesis. In order to detect MMP-9 and IL-6 concentrations with high sensitivity and specificity, an efficient microfluidic-SERS sensing system was prepared based on surface-enhanced Raman scattering (SERS). The aptamer recognition-release mechanism and the dual signal amplification strategy were applied in the sensing system. The sensor system was developed using two kinds of nanomaterials with excellent SERS properties, namely gold-coated iron tetroxide particles (Fe3O4@AuNPs) and gold nanocages (AuNCs). In addition, Fe3O4@AuNPs also has magnetic adsorption properties. In the sensing system, single-stranded DNA1 (ssDNA1) and aptamer were modified on Fe3O4@AuNPs. Single-stranded DNA2 (ssDNA2) and Raman tags were modified on AuNCs. When the target was present, the aptamer bound to the target and detached from the Fe3O4@AuNPs, andssDNA2 bound to the exposed ssDNA1. At this time, the Fe3O4@AuNPs@AuNCs@SERS tag complex was formed, and the SERS signal was enhanced for the first time. Under the action of an external magnet on the microfluidic chip, the complex was magnetized and enriched. The SERS signal was enhanced for the second time. Due to the high affinity between the aptamer and the target object, the sensing system has a strong specificity. The double amplification of the SERS signal gave the system excellent sensitivity. The limit of detection (LOD) relative to MMP-9 and IL-6 were as low as 0.178pg/mL and 0.165pg/mL, respectively. The microfluidic-SERS sensing system has a feasible prospect in the early screening of gastric cancer.

Isoorientin Improves Excisional Skin Wound Healing in Mice

Background/Objectives: Wound healing relies on a coordinated process with the participation of different mediators. Natural products are a source of active compounds with healing potential. Isoorientin is a natural flavone recognized as having several pharmacological properties, such as anti-inflammatory effects, making it a potential treatment for wounds. We investigated the effect of isoorientin on the healing of excisional skin wounds. Methods: Male Swiss mice were subjected to the induction of excisional skin wounds (6 mm diameter) and treated with a vehicle (2% dimethyl sulfoxide in propylene glycol) or 2.5% isoorientin applied topically once a day for 14 days. The wound area was measured on days 0, 3, 7, and 14. Histopathological analyses were performed on the cicatricial tissue after 14 days. The myeloperoxidase activity and the interleukin-1β, tumoral necrosis factor (TNF)-α, and interleukin-6 concentrations were determined on the third day. Results: We observed that 3 days after the topical application of isoorientin, the lesion area was significantly smaller when compared to those of the vehicle (p &lt; 0.01) and control (p &lt; 0.05) groups. No difference was observed after 7 and 14 days of induction. Despite this, on day 14, histological analysis of cicatricial tissue from the animals treated with isoorientin showed reduced epidermal thickness (p &lt; 0.001) and increased collagen deposition (p &lt; 0.001). These effects were accompanied by decreased myeloperoxidase activity and interleukin-1β concentration on the third day of induction, without alteration in TNF-α and interleukin-6. Conclusions: The treatment with isoorientin promoted better tissue repair in excisional wounds in mice, which may be linked to the modulation of the early inflammatory response.

The Impact of Negative Energy Balance in Holstein-Friesian Cows on the Blood Concentrations of Interleukin-6 and Plasminogen.

Background/Objectives: The negative energy balance activaties of spontaneous lipolysis. This may promotes inflammation within the adipose tissue. The aim of the study was to explain the development of inflammation during increased lactogenesis. It was hypothesized that lipolysis contributes synthesis of interleukin-6 and plasminogen. Methods: The study was in production conditions carried out using Holstein-Friesian cows. The period studied covered time of early lactation. Results: Up to the peak of lactation, milk yield strongly influenced the rate of loss of body condition. This had an impact on with the intensity of the release of the fatty acids. In both cases this relationships strengthened to the peak of production. Oobserved tendencies towards a decrease in the concentration of glucose and an increase in that of leptin. Loss of the body condition and the release of NEFA were were influencing to affect the blood concentrations of interleukin-6 and plasminogen. We have shown that IL-6 has a relatively strong correlation with the NEFA. They correlate with IL-6 independently of EB influence. This may suggest independent associations between these variables, which could potentially be applied in practice. Conclusions: The NEFA release in the long term can increase the inflammatory response within adipose tissue and can intensify the release of interleukin-6 and plasminogen. It is likely that in the initial stage of lactogenesis, the inflammatory process developing within adipose tissue is physiologically justified. Our results can provide background to this little-described area of research.

Baseline level of interleukin-6 is associated with the risk of acute coronary syndrome development in SARS-CoV‐2 infection

BackgroundAcute coronary syndrome (ACS) is frequently reported in patients with coronavirus disease 2019 (COVID-19). Cytokine storm induced by interleukin-6 (IL-6) has been suggested to potentially cause myocardial injury in COVID-19. We investigated the association between baseline level of IL-6 and development of ACS in COVID-19 patients.MethodsDemographic and clinical data of hospitalized COVID-19 patients from 2020 to 2022 were reviewed. Extracted data including patient characteristics, laboratory biomarkers, and systemic inflammation indexes in patients with or without ACS were reviewed and analyzed. Logistic regression models were applied to analyze predictors of ACS development and receiver-operating characteristic (ROC) curves were used to assess discriminatory power of IL-6 and other risk factors for predicting ACS development.ResultsAmong 1,753 COVID-19 patients, 37 cases experienced ACS and 159 patients without main COVID-19 complications were randomly selected as controls. ACS patients were older (p = 0.001) and suffered from more comorbidities including diabetes (43% vs. 18%, p = 0.001), hypertension (40.5% vs. 24.5%, p = 0.050), ischemic heart disease (49% vs. 9%, p = 0.001), and hyperlipidemia (19% vs. 5%, p = 0.010). Also, decreased level of consciousness (31.6% vs. 2.5%, p = 0.001), ICU admission (65% vs. 2%, p = 0.001), and mortality events (70% vs. 0.6%, p = 0.001) were more prevalent in the ACS group. Baseline levels of IL-6 (p = 0.001), D-dimer (p = 0.026), troponin (p = 0.001), blood urea nitrogen (p = 0.002), and creatinine (p = 0.008) were higher in ACS patients but erythrocyte sedimentation rate (p = 0.013), hemoglobin (p = 0.033), and red blood cells (p = 0.028) were lower compared with controls. Also, age (OR: 1.06, p = 0.019), IL-6 (OR: 1.44, p = 0.047), and cardiovascular disease (CVD) (OR: 3.66, p = 0.043) were associated with ACS development. The area under the curve (AUC) of IL-6 and combined predictors respectively was 0.661 (p = 0.002) and 0.829 (p = 0.001).ConclusionsHigh IL-6 concentration at baseline is a strong predictor for ACS development in COVID-19 patients. Also, elderly and concurrent CVD are significantly associated with ACS development.

Platelet-rich plasma ameliorates cartilage degradation in rat models of osteoarthritis via the OPG/RANKL/RANK system.

Osteoarthritis (OA) is one of the most common degenerative joint diseases in the elderly, which is featured by the degradation of articular cartilage. Recently, platelet-rich plasma (PRP) injection into the affected joint has become one biological therapy for OA treatment. The OPG/RANKL/ RANK signalling has been reported to mediate OA progression. Our study aimed to confirm whether PRP injection retards OA development through the regulation of the OPG/RANKL/RANK system. The OA rat models were induced by medial menisci resection combined with anterior cruciate ligament transection. Four weeks after surgery, OA-induced rats received intra- articular injection with 50 μL PRP once a week for 6 weeks. Rats were euthanised one week after the 6th injection. Rat knee joints were subjected to histopathological examination by haematoxylin- eosin (H&E) and safranin O staining. Osteoprotegerin (OPG), receptor activator of nuclear factor kappa B (RANK), and RANK ligand (RANKL) in the articular cartilage of rats were tested through immunofluorescence staining and western blotting. Serum interleukin-1β (IL-1β) and interleukin-6 (IL-6) levels were measured by enzyme-linked immunosorbent assay (ELISA). Matrix metalloproteinase- 13 (MMP-13), aggrecan, collagen α, IL-1β, IL-6, tumour necrosis factor-alpha (TNF-α), and nuclear factor kappa-B (NF-κB) mRNA and protein expression in rat articular cartilage were examined by real-time quantitative polymerase chain reaction (RT-qPCR) and western blotting, respectively. Intra-articular injections of PRP significantly improved the structural integrity of the articular cartilage and enhanced the synthesis of glycosaminoglycans. PRP reduced MMP-13 protein level but increased aggrecan and collagen α protein levels in articular cartilage of OA rats. OA-induced increase in serum IL-1β, IL-6, and TNF-α concentrations as well as increased MMP-13, and decreased collagen II mRNA levels were reversed by the administration of PRP. OA increased IL-1β, TNF-α, and NF-κB mRNA expression in rat articular cartilage whereas PRP administration ameliorated these changes. Moreover, in the articular tissue of OA-induced rats the increased OPG protein level was further elevated by PRP injections whereas the protein level of RANK did not change. The increase in the protein level of RANKL in OA-induced articular tissue was offset by PRP administration. PRP elevated OPG mRNA expression and the OPG/RANKL mRNA ratio, but reduced RANKL mRNA expression and the RANKL/RANK mRNA ratio in the articular tissue of OA-induced rats. PRP mitigates cartilage degradation and inflammation in experimental knee OA by regulating the OPG/RANKL/RANK signalling system.

A randomized controlled cross-over trial investigating the acute inflammatory and metabolic response after meals based on red meat, fatty fish, or soy protein: the postprandial inflammation in rheumatoid arthritis (PIRA) trial.

Rheumatoid Arthritis (RA) has a point prevalence of around 20million people worldwide. Patients with RA often believe that food intake affects disease activity, and that intake of red meat aggravate symptoms. The main objective of the Postprandial Inflammation in Rheumatoid Arthritis (PIRA) trial was to assess whether postprandial inflammation and serum lipid profile are affected differently by a meal including red meat, fatty fish, or a soy protein (vegan) meal. Using a randomized controlled crossover design, 25 patients were assigned to eat isocaloric hamburger meals consisting of red meat (60% beef, 40% pork), fatty fish (salmon), or soy protein for breakfast. Blood samples were taken before meals and at intervals up to 5h postprandial. The analysis included the inflammation marker interleukin 6 (IL-6) and serum lipids. No significant differences in postprandial IL-6 or triglyceride concentrations were found between meals. However, the area under the curve of very low density lipoprotein (VLDL) particle counts, as well as VLDL-4-bound cholesterol, triglycerides, and phospholipids, was higher after the fatty fish compared to both red meat and soy protein. Postprandial inflammation assessed by IL-6 did not indicate any acute negative effects of red meat intake compared to fatty fish- or soy protein in patients with RA. The fatty fish meal resulted in a higher number of VLDL-particles and more lipids in the form of small VLDL particles compared to the other protein sources.

Association of serum and synovial adipokines (chemerin and resistin) with inflammatory markers and ultrasonographic evaluation scores in patients with knee joint osteoarthritis- a pilot study.

Chemerin and resistin are adipokines studied as potential markers for early diagnosis and disease severity in patients with knee osteoarthritis (KOA) Therefore, we aimed to investigate the associations serum and synovial levels of chemerin and resistin with inflammatory parameters and ultrasonographic scores (US) in KOA individuals. Serum was collected from 28 patients with KOA and synovial fluid was obtained from 16 of them. Another 31 age and sex matched cases with no joint disease were included as healthy controls. Concentrations of chemerin, resistin, interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) were determined with ELISA. Erythrocyte sedimentation rate (ESR), C-reactive protein, serum uric acid (UA) were measured in the patients group. Participants with KOA underwent US assessment using the Outcome Measures in Rheumatology (OMERACT) scores. Patients with KOA had statistically significant higher level of serum resistin than healthy controls [11.05 (3.78-24.13) ng/mL and 7.23 (3.83-12.19) respectively, p < 0.001]. A strong correlation was found between serum chemerin and ESR (r = 0.434, p = 0.021), uric acid (r = 0.573, p = 0.001) as well as the US (r=-0.872, p < 0.001). Serum resistin demonstrated significant association with TNF-alpha (r = 0.398, p = 0.044). In conclusion, both chemerin and resistin might contribute to inflammatory changes associated with KOA. Further studies are needed to elucidate their potential role in the pathogenesis of the disease.

Role the (IL1, IL6, and TNF) with Chronic Autoimmune Diseases in Mosul City / Iraq

Objective: Our study examined the relationship of the levels of cytokines IL1, 6, and TNF in three different immune diseases with age and Sex. Material and methods: The samples of the study were obtained from in Mosul city hospitals for the period from October 2023 to February 29, 2024. The study included 90 different medical cases suffering from immune diseases, 50 of whom were suffering from rheumatoid arthritis, 16 were suffering from erythematosus, and 24 were suffering from Celiac disease. The ages of the study participants were between 10 years and 65 years. Outcomes: Serum samples were examined for IL1, 6, and TNF using the ELISA technique. The results of ELISA revealed that Concentrations of Interleukins and TNF were low in all patients because the patients in the chronic phase of Autoimmune Diseases take treatment to reduce the cytokines which is hyperactive Therefore, cytokines concentrations appeared lower than standard concentrations. However, the results show a significant association between measuring IL-1 for a CD and measuring IL-6, TNF for an SLE among Autoimmune disease patients and their sex, and age. Conclusion: significance and impact of study: IL1, 6, and TNF are one of the most common cytokines on the globe. It has been connected directly or indirectly with various disorders, including autoimmune diseases. However, the link between IL1, 6 - TNF and Autoimmune Diseases is still controversial. Our results indicate that they play a possible role in the development of autoimmune diseases; however, more studies on a larger scale are required to confirm the results.