Higher Interleukin-6 Levels Research Articles

Metabolomics and frailty: a "from bench to bedside" approach to atrial fibrillation in older patients

Abstract Background Atrial fibrillation (AF) is the most common sustained arrhythmia diagnosed at an advanced age. The most important complications of AF are stroke, heart failure and dementia. The pathophysiology of the arrhythmia is complex and multifaceted and several aspects are still not completely understood. Purpose Our project aimed at exploring the molecular characteristics of AF in older patients using an untargeted metabolomics approach, an analytical technique that provides an insight of the global metabolic profile at an individual level. As secondary endpoints, we evaluated the association between metabolomics and acylcarnitines, which are mediators of myocyte electrical instability, and difference in metabolomics profile between healthy controls (C) and AF patients (AF-P). Method We evaluated 50 consecutive older AF-P with persistent AF, waiting to be treated with elective electrical cardioversion of the arrhythmia, and 22 healthy controls (C). In all patients, the cardiological evaluation was integrated with tools of the Geriatric Multidimensional Assessment (GMA) to describe neurocognitive function (Mini-Mental State Examination, MMSE), depressive symptoms (15-item Geriatric Depression Scale, GDS), and physical performance (Short Physical Performance Battery, SPPB). Interleukin-6 (IL-6), a marker of low-grade inflammation, was measured with ELISA assays. Metabolomics analysis and acylcarnitine measurements were carried out using gas chromatography coupled with mass spectrometry (GC-MS). Results AF-P and C did not differ by age (76 ± 6 vs. 70 ± 14 years, p = 0.055); patients had a lower proportion of women (AF-P: 32% vs. C: 64%, p = 0.012). Cluster analysis applied to metabolomic data in all population identified two subset of subjects, characterized by a different body mass index (BMI; 23.57 vs. 32.53 Kg/m², p = 0.046). When studying only the AF-P group, the simultaneous presence of a higher CHA2DS2-VASc score (4.17 ± 1.32 vs. 2.88 ± 1.83, p = 0.007), a lower physical function (SPPB; 8.97± 2.22 vs. 10.75 ± 1.13, p = 0.009), and higher IL-6 levels (4.42 vs. 2.39 pg/mL, p = 0.002) described the cluster with a worse clinical phenotype and a specific metabolomics pattern. Furthermore, an association between IL-6 and medium- long-chain acylcarnitines emerged (acylcarnitine 12:1, β = 31.7 ± 9.4, R = 0.446, p = 0.001). Conclusions Present analysis demonstrated that a specific metabolomics profile was characteristic of older AF patients with a frail phenotype, identified by higher CHA2DS2-VASc score and IL-6 concentration, and lower physical performance. Future studies are needed to reveal the single molecular pathways responsible of these behaviour, potentially useful to guide a targeted therapy. Last, inflammation per se could contribute to electrical instability in AF, while body mass index, a surrogate measure of undernutrition, could identify different metabolic pathways in controls and in patients with the arrhythmia.Metabolomics by clinical phenotypes

Abstract 13711: Clonal Hematopoiesis Driven by TET2 and ASXL1 but Not DNMT3A is Associated With Interleukin 6 Levels, Cardiac Biomarkers, Cardiac Remodeling, and Risk of Atrial Fibrillation

Introduction: Aging and inflammation are associated with risk of atrial fibrillation (AF), to which clonal hematopoiesis of indeterminate potential (CHIP) may contribute. We investigated whether CHIP was associated with AF, inflammatory and cardiac biomarkers and cardiac structural changes. Methods: We ascertained CHIP (variant allele frequency, VAF ≥2%) in the Atherosclerosis Risk in Community Study (ARIC visit-5, n = 4,131) and the UK Biobank (UKBB, n = 195,851) participants. Using multivariable Cox regression models, we studied the association of CHIP and the top three implicated genes (i.e., DNMT3A , TET2 , ASXL1 ) with incident AF and conducted a meta-analysis on both cohorts. We also ascertained high-sensitivity C-reactive protein (hs-CRP), interleukin 6 (IL6), IL18, high-sensitivity troponin T and I (hs-TnT and hs-TnI), NT-proBNP, and echocardiography indices in ARIC. We first standardized the natural log of all markers (st-ln) and used the adjusted quantile regression to compare the median in those with and without CHIP. Results: In ARIC, the mean ± SD age was 75.8 ± 5.2 years, 41% were men, 23% were Black, 25% had CHIP, and 11.6% had large CHIP (VAF ≥10%). These measures in UKBB were 56.4 ± 8.1 years, 45%, 2%, 5.8%, and 2.6%, respectively. In the meta-analysis, compared to those without CHIP, the hazard ratios (95% confidence interval) for AF were 1.12 (1.01 - 1.25, P =0.035), 1.31 (1.07 - 1.60, P =0.009), and 1.48 (1.05 - 2.08, P =0.026) for Large-CHIP, Large- TET2, and Large- ASXL1 , respectively. hs-CRP and IL18 levels were similar in those with and without CHIP as well as gene-specific subgroups. Large- TET2 and ASXL1 were associated with higher IL6, which was separately associated with AF. Additionally, Large- ASXL1 was associated with increased left ventricle mass index and NT-proBNP (coefficients in Figure 1 ). Conclusion: Large TET2 and ASXL1 but not DNMT3A CHIP is associated with higher IL6 levels, indices of cardiac remodeling, and an increased risk of AF.

Immunogenicity of extracellular proteins of Flavobacterium covae in Ictalurus punctatus

BackgroundColumnaris disease, instigated by Gram-negative Flavobacterium covae (F. covae), is a dreadful disease of many different genera of freshwater fish with alarmingly high mortality rates. Ictalurus punctatus (I. punctatus) is extremely prone to this disease. Despite the terrible implications of this disease, very little is known about how the host and the bacterium's virulence factor interact. Secreted extracellular proteins (SEPs) are key bacterial virulence agents that frequently provide immunogenicity. In a previous study, the major secreted extracellular proteins of F. covae were identified and their protective efficacy was verified in I. punctatus, and the results were published. In the current study, an endeavor has been made to examine the progressive shifts in I. punctatus immunity following immunization with F. covae SEPs in order to more thoroughly comprehend the host's intrinsic and acquired immune responses against F. covae infection. An enzyme-linked immunosorbent test (ELISA) is operated to analyze specific humoral immune responses against SEPs of F. covae. Moreover, the expressions of immune-associated genes that are related to inherent and acquired immunity were monitored in the anterior kidneys and spleens of the vaccinated I. punctatus.ResultsMarked rise in immunoglobulin M (IgM) levels were detected in the serum of I. punctatus vaccinated with different SEP formulations, including crude SEPs, heat-deactivated SEPs, and SEPs combined with adjuvant, at 14 and 21 days post-vaccination. At the same time points, a marked increase in the expression levels of clusters of differentiation (CD4-1 and CD8-β) and major histocompatibility complex (MHC-II) genes was detected in the vaccinated fish's anterior kidneys and spleens, while the highest levels of interleukin-8 (IL-8) and tumor necrosis factor alpha (TNF-α) up-regulations were detected in the immunized fish's anterior kidneys 14 days following vaccination.ConclusionsThis work revealed that SEPs are an effective basis for vaccination against F. covae infection, eliciting humoral and inherent immune responses of I. punctatus after SEPs immunization. Improvements are needed to further enhance the I. punctatus immunological responses to SEPs of F. covae since these antigens remain a prospective candidate for future optimization and clinical trials in aquaculture settings.

Dynamic changes in inflammatory responses and 3-year clinical outcomes of XINSORB scaffolds in coronary stenting

BackgroundInflammation is known to play a crucial role in the development of coronary atherosclerosis and vascular healing after stenting. This study aimed to investigate the dynamic changes in inflammatory responses between XINSORB and TIVOLI scaffolds and their correlation with 3-year clinical outcomes. MethodA total of 140 patients in the XINSORB group and 42 patients in the TIVOLI group were included in this prospective, single-center study, conducted in Shanghai tenth People's Hospital. Blood samples were collected at baseline, 24 h, 6 months, and 12 months after stent implantation to measure high sensitivity C-reactive protein (hsCRP), fibrinogen (FBG), white blood cell count (WBC), tumor necrosis factor (TNF), and interleukin-6 (IL-6). Receiver-operating characteristic curves and proportional hazards models were generated to evaluate the relationship between 24-h postoperative inflammatory indicators and 3-year patient-oriented composite endpoints (POCE). ResultThe levels of hsCRP, FBG, WBC, TNF, and IL-6 reached their peak levels 24 h after stenting and then gradually decreased to levels comparable to baseline at 6 and 12 months. During the 3-year follow-up, 11.4 % of the XINSORB cohort and 9.5 % of the TIVOLI cohort experienced POCE (P = 0.948). High levels of hsCRP and IL-6 24 h after the procedure were associated with clinical endpoints, and the combination of these two biomarkers improved the predictive ability of prognosis. ConclusionsThere were no significant differences between the changes in the concentration of inflammatory biomarkers after XINSORB stents or drug-eluting stent implantation. Reduction in postoperative inflammatory levels may decrease the occurrence of clinical outcomes. This study provides insights into the dynamic changes of inflammatory responses and their correlation with clinical outcomes, which could have implications for the management of patients undergoing coronary stenting. Trial registrationThe study has been registered on the official website of the China Clinical Trial Registry (ChiCTR1800014966).

SAPHO syndrome: current clinical, diagnostic and treatment approaches.

This review provides an overview of SAPHO (Synovitis, Acne, Pustulosis, Hyperostosis, and Osteitis), a rare autoinflammatory disease that primarily affects bones, skin, and joints. We conducted a search on Medline/PubMed using keywords such as SAPHO syndrome, chronic recurrent multifocal osteitis/osteomyelitis, and related terms. SAPHO syndrome is rare, with a reported frequency of 1 in 10,000 in the Caucasian population. However, the actual incidence of SAPHO syndrome is unknown, and the incidence of the disease is likely higher. The pathogenesis of SAPHO syndrome remains incompletely understood. Current evidence suggests that SAPHO results from a complex interplay between immune dysregulation, genetic susceptibility, and environmental factors. It's not clear if SAPHO syndrome is an autoimmune disease or an autoinflammatory disease, but current evidence suggests that it's more likely an autoinflammatory disease because of things like neutrophil hyperactivity, fewer natural killer (NK) cells, high levels of interleukin (IL)-1, and a good response to treatments that block IL-1. Osteo-articular (OA) involvement is a key clinical feature of SAPHO. It affects the anterior chest wall, axial skeleton, peripheral joints, mandible, long bones of the extremities, and pelvis. Dermatological involvement is a common target in SAPHO, with lesions observed in 60-90% of cases. Common skin lesions include psoriasis and acne, with hidradenitis suppurativa and neutrophilic dermatoses being less commonly seen. Other clinical findings include constitutional symptoms caused by systemic inflammation, such as fever, weight loss, and fatigue. There is no specific laboratory finding for SAPHO syndrome. However, during active disease, there may be an increase in positive acute phase markers, such as erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), complement levels, mild leukocytosis, and thrombocytosis. Diagnosis is crucial for SAPHO syndrome, which lacks a specific diagnostic finding and is often underrecognized. A comprehensive evaluation of a patient's medical history and physical examination is crucial. Treatment options include non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, conventional and synthetic disease-modifying agents (cDMARDs and sDMARDs), biological therapies, bisphosphonates, and antibiotics. Biological treatments have emerged as a viable alternative for SAPHO patients who do not respond to conventional treatments.

IL-6 serum level, ARDS, and AKI as risk factors for the COVID-19 infection's mortality in children.

Dysregulated immune responses are developed in Coronavirus disease-2019 (COVID-19) and Interleukin-6 (IL-6) levels are reflecting the severity of the clinical presentation. This study aimed to analyze IL-6 serum level, Acute Respiratory Distress Syndrome (ARDS), and Acute Kidney Injury (AKI) as risk factors for mortality in children with COVID-19. This prospective cohort study was conducted on children with COVID-19 infection confirmed by Real Time Polymerase Chain Reaction (RT-PCR) who were admitted to infection center at Dr. Wahidin Sudirohusodo Hospital from September 2021 to September 2022. Subjects were selected using the consecutive sampling method. A total of 2,060 COVID-19 RT-PCR tests were performed, and 1,065 children were confirmed positive. There were 291 cases that met the inclusion criteria, with 28.52 percent non-survives and 71.48% survives. The risk factors for mortality were IL-6, ARDS, AKI, Prothrombin Time / Activated Partial Thromboplastin Time (PT/aPTT), oxygen saturation, Absolut lymphocyte count (ALC), leukocytes, Length of Stay (LOS), and nutritional status (p<0.05). IL-6 levels increased in all patients (23.48-252.58 pq/ml). COVID-19 patients with AKI, ARDS, low oxygen saturation and thrombocytopenia had the highest levels of IL-6 (p 0.05). The IL-6 cut-off point was >80.97 pg/ml with 93% sensitivity and 90% specificity. Area Under Curve was 0.981 (95% CI), 0.960-1.000). A multivariate analysis showed IL-6 levels with OR 18.570 (95% CI 5.320-64.803), ARDS with Odds Ratio (OR) 10.177, (95% Confidence Interval (CI) 1.310-9.040), and AKI with OR 3.220 (95% CI 1.070-10.362). A combination of increased IL-6, ARDS, and AKI can predict a mortality probability as high as 98.3%. IL-6, ARDS, and AKI are risk factors for mortality in children with COVID-19. IL-6 level was the highest mortality risk factor.

Effect of interleukin-12 gene expression on insulin resistance in patients with acne vulgaris.

Insulin resistance (IR) is a condition where cells become resistant to insulin, causing impaired glucose uptake and increased blood glucose levels. Interleukin-12 (IL-12), a cytokine, regulates the immune system. High levels of IL-12 can lead to chronic inflammation, exacerbate resistance to insulin, and contribute to type 2 diabetes. Also, link IR to acne vulgaris (AV), as it reduces tissue sensitivity to insulin, causing increased insulin levels and sebum production, which can contribute to acne development. To explore the role of IL-12 gene expression on IR in AV patients and to study the role of IL-12 gene in the development of AV. A case-control study was performed on 68 AV patients and 68 healthy controls. The biochemical analysis included fasting glucose, fasting insulin, (HOMA-IR), and serum IL-12 level. IL-12 gene expression was performed by quantitative real-time PCR for both two groups. In addition, folding change was calculated by using the standard 2-(∆∆Ct) method. IL-12 level, IL-12 folding change, fasting insulin, and IR were all increased in acne patients. A highly significant linear correlation was found between IL-12 folding change and both IL-12 levels and IR. There is a substantial positive significant simple linear association between IL-12 level and IL-12 folding change, as well as IR and IL-12 folding change, in moderate and severe acne. IL-12 gene has an important role in IR and the development of acne in AV patients.

Indications of pro-inflammatory cytokines in laparoscopic and open liver resection for early-stage hepatocellular carcinoma

BackgroundOur clinical practice of laparoscopic liver resection (LLR) had achieved better short-term and long-term benefits for patients with hepatocellular carcinoma (HCC) over open liver resection (OLR), but the underlying mechanisms are not clear. This study was to find out whether systemic inflammation plays an important role. MethodsA total of 103 patients with early-stage HCC under liver resection were enrolled (LLR group, n = 53; OLR group, n = 50). The expression of 9 inflammatory cytokines in patients at preoperation, postoperative day 1 (POD1) and POD7 was quantified by Luminex Multiplex assay. The relationships of the cytokines and the postoperative outcomes were compared between LLR and OLR. ResultsSeven of the circulating cytokines were found to be significantly upregulated on POD1 after LLR or OLR compared to their preoperative levels. Compared to OLR, the POD1 levels of granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-6 (IL-6), IL-8, and monocyte chemoattractant protein-1 (MCP-1) in the LLR group were significantly lower. Higher POD1 levels of these cytokines were significantly correlated with longer operative time and higher volume of blood loss during operation. The levels of these cytokines were positively associated with postoperative liver injury, and the length of hospital stay. Importantly, a high level of IL-6 at POD1 was a risk factor for HCC recurrence and poor disease-free survival after liver resection. ConclusionsSignificantly lower level of GM-CSF, IL-6, IL-8, and MCP-1 after liver resection represented a milder systemic inflammation which might be an important mechanism to offer better short-term and long-term outcomes in LLR over OLR.

Exploring Prognostically Significant Factors in COVID-19-Associated Pulmonary Fibrosis after Adaptive Lung Ventilation.

Research data on hospitalized coronavirus 2019 (COVID-19) survivors indicate the persistence of symptoms, radiological abnormalities, and physiological disorders months after the initial infection. Given the scale of the ongoing pandemic, a substantial number of patients with severe residual pulmonary fibrosis (PF) and oxygen dependence are anticipated. Currently, the search for risk factors associated with the development of fibrotic radiological abnormalities after moderate to severe COVID-19 is underway. Furthermore, the extent to which computed tomography (CT) data correlate with postdischarge symptoms and physical functions remains unclear. This study aimed to characterize patients experiencing persistent pulmonary consequences after hospital discharge. We examined clinical, radiological, and laboratory predictors of pulmonary fibrosis after COVID-19 infection. We retrospectively evaluated fibrosis-like lung changes and their prognostic factors in COVID-19 survivors. Our study included 77 patients with laboratory-confirmed COVID-19 who received inpatient treatment at City Clinical Hospital No. 1 in Almaty between November and December 2020. We assessed patients during the acute phase of the disease and again 6 to 8 months after discharge using high-resolution computed tomography (CT). Patients were classified into 2 cohorts based on semi-quantitative analysis of subsequently added tomograms-those with radiological fibrosis-like abnormalities (main group) and those who had recovered (control group). Parenchymal cords, irregular interfaces, reticulation, and traction bronchiectasis were common CT findings among all COVID-19 patients. Our study focused on patients who developed pulmonary fibrosis within 1 month after the onset of the disease. After 6 to 8 months, fibrosis-like lung changes persisted in 49.35% of patients (leading group), while 50.65% showed disease resolution (control group). Age, body mass index, high interleukin-6 (IL-6) levels, low IO levels, and the need for mechanical ventilation were identified as prognostic indicators for the persistence of pulmonary fibrosis. Our study revealed that pulmonary function can return to normal in over half of COVID-19 patients 8 months after infection onset. Despite advancements in COVID-19 treatment, there remains a significant knowledge gap in managing long-term effects, especially pulmonary fibrosis. Continued clinical trials and research on post COVID-19 fibrosis are essential to prevent early mortality due to the long-term impacts on these patients.

Chylothorax after chimeric antigen receptor T cell therapy for relapsed and refractory diffuse large B-cell lymphoma: A case report.

Anti-CD19-targeted chimeric antigen receptor (CAR) T cell therapy is effective in treating relapsed/refractory diffuse large B-cell lymphoma (DLBCL). This therapy is associated with several side effects that can be life-threatening such as cytokine release syndrome (CRS). However, chylothorax associated with CRS after CAR-T therapy has not been reported. A 23-year-old male diagnosed with DLBCL relapsing after autologous peripheral blood stem cell transplantation was treated with anti-CD19-targeted CAR-T cell therapy. After CAR-T cell transfusion, he developed grade 3 CRS includes fever, dyspnea, tachycardia and hypotension. The symptoms of CRS persisted and chest plain film revealed bilateral pleural effusion. Chylothorax was confirmed by the pleural effusion analysis that triglyceride level was 1061 mg/dL. Bacterial and fungal culture of pleural fluid reported no pathogen was detected. Cytological examination of pleural effusion revealed no malignant cells. The chylothorax resolved after treatment with intravenous administration of tocilizumab. On 30-day follow-up, the patient was in stable clinical condition with complete remission of DLBCL on whole-body positron emission tomography scan. We reported a rare case of CAR-T associated chylothorax in a patient with relapsed and refractory DLBCL. Grade 3 CRS with high interleukin-6 level was presented in our patient. The symptoms of CRS were improved with tocilizumab treatment and the chylothorax resolved later on. It is suggested that high interleukin-6 releases might induce chyle leakage resulting from activations of endothelium and coagulation. Our finding highlights the occurrence of chylothorax during the course of CAR-T cell therapy and the importance of proper monitoring and prompt management of this life-threatening side effect.

Contribution of T helper 17 cells and interleukin-17 to the pathogenesis of primary immune thrombocytopenia in Egyptian children

Though pathogenesis of primary immune thrombocytopenia (ITP) is still rendered unclear, yet there are many research efforts that have been directed to the role of T helper 17 (Th17) and interleukin 17 (IL-17) in the pathogenesis of this disease. The Th17 cell, which produces IL-17, is a subset of T helper cells. Interleukin 17 is pro-inflammatory cytokine that is recently proved to have a crucial role in the emergence of autoimmune diseases. We aimed to investigate the role of T helper17 cells and interleukin-17 in the pathogenesis of ITP in Egyptian children. This study was carried out on 100 children with ITP and 100 apparently healthy children as a control group. Patients were subjected to full medical history taking, thorough physical examination and routine investigations according to our local standards. Percentage of Th17 cells was measured by flow cytometry in study groups. Also, serum IL-17 was measured in in study groups by ELISA. Th 17 cells were significantly higher in patients compared to controls. Moreover, 3.1-fold increased serum levels of IL-17 were observed in patients with ITP compared to controls. Newly diagnosed patients had significantly higher percentage of Th-17cells as well as higher IL-17 levels than patients with either persistent or chronic ITP. Conclusion: We concluded that Th 17 cells and IL-17 seem to play an important role in the pathogenesis of ITP in Egyptian children.What is Known -- What is New:• The pathogenesis of ITP is heterogeneous A novel subset of CD4+ T cells, distinct from Th1 and Th2, was recently identified. It is characterized by the production of IL-17 and, therefore, designated as Th17 cells. Several studies support a pivotal role for serum cytokines in the pathogenesis of ITP and provide evidence to suggest that helper Tlymphocytes polarize into Th1 and Th2 immune response. we aimed to investigate the role of T helper17 cells and interleukin-17 in the pathogenesis of ITP in Egyptian children.

Lineage origin and transcriptional control of autoantigen-specific T-regulatory type 1 cells.

T Regulatory type-1 (TR1) cells represent an immunosuppressive T cell subset, discovered over 25 years ago, that produces high levels of interleukin-10 (IL-10) but, unlike its FoxP3+ T regulatory (Treg) cell counterpart, does not express FoxP3 or CD25. Experimental evidence generated over the last few years has exposed a promising role for TR1 cells as targets of therapeutic intervention in immune-mediated diseases. The discovery of cell surface markers capable of distinguishing these cells from related T cell types and the application of next generation sequencing techniques to defining their transcriptional make-up have enabled a more accurate description of this T cell population. However, the developmental biology of TR1 cells has long remained elusive, in particular the identity of the cell type(s) giving rise to bona fide TR1 cells in vivo. Here, we review the fundamental phenotypic, transcriptional and functional properties of this T cell subset, and summarize recent lines of evidence shedding light into its ontogeny.

Relationship between Disease Characteristics and Circulating Interleukin 6 in a Well-Characterized Cohort of Patients with Systemic Lupus Erythematosus.

Interleukin-6 (IL-6) is a proinflammatory cytokine that mediates pleiotropic functions in immune responses and inflammatory diseases. The literature lacks studies, with a clinical perspective, on the relationship between IL-6 serum levels and the characteristics of the disease in patients with systemic lupus erythematosus (SLE). In the present work, we aimed to analyze the association between circulating IL-6 and disease manifestations in a well-characterized series of patients with SLE. Serum IL-6 levels and disease activity (SLEDAI-2K), severity (Katz) and damage index (SLICC-DI), complete lipid profile, and subclinical carotid atherosclerosis were evaluated in 284 patients with SLE. In addition, a complete characterization of the complement system was performed in samples from patients with SLE. A multivariate linear regression analysis was carried out to study the relationship between clinical and laboratory characteristics of the disease and IL-6 levels. Age (beta coef. 0.07 [95%CI 0.01-0.1] pg/mL, p = 0.014), C-reactive protein (beta coef. 0.21 [95%CI 0.16-0.25] pg/mL, p < 0.01), and male gender (beta coef. 2 [95%CI 0.3-0.5] pg/mL, p = 0.024), were positively associated with higher IL-6 levels in SLE patients. Most disease characteristics and damage and activity indices did not show significant relationships with IL-6. However, after multivariate analysis, IL-6 was associated with lower serum levels of HDL cholesterol (beta coef. -0.04 [95%CI -0.08-(-0.1)] pg/mL, p = 0.011), and apolipoprotein A1 (beta coef. -0.02 [95%CI -0.04-(-0.001)] pg/mL, p = 0.035). In contrast, the alternative complement cascade, C1inh, and C3a were all positively and independently associated with higher serum levels of IL-6. Moreover, stratification of the Systematic Coronary Risk Assessment 2 (SCORE2) results according to different categories of cardiovascular risk was associated with higher circulating serum IL-6 levels (beta coef. 0.2 [95%CI 0.02-0.4], pg/mL, p = 0.028). In conclusion, in a large series of SLE patients, IL-6 was not associated with disease-related features of SLE, including damage, severity, or activity indices. However, an association was found between serum IL-6 levels and circulating C3a and cardiovascular risk. Our study emphasizes the importance that IL-6 could have in cardiovascular disease and complement system disruption of SLE patients. Therapies targeting IL-6 could have a role in these two clinical manifestations of patients with SLE.

Nonlinear Relationship Between Interleukin-6 and NT-proBNP at Admission in Hospitalized COVID-19 Patients.

Elevated levels of the inflammatory marker interleukin-6 (IL-6) and cardiac injury marker N-terminal pro-B-type natriuretic peptide (NT-proBNP) have been observed in patients with coronavirus disease 2019 (COVID-19). However, the relationship between IL-6 and NT-proBNP levels remains unclear. Therefore, we investigated the relationship between IL-6 and NT-proBNP levels in patients with COVID-19. This was a cross-sectional study. Consecutive patients with COVID-19 were included herein. The independent and dependent target variables were the IL-6 and NT-proBNP levels, respectively, measured at baseline. Univariate andmultivariate linear regression analyses and curve fitting were also performed. The average age of the 121 selected participants was 49.8 ± 15.8 years old, and 48.8% (59/121) were male. The estimated β value between Ln-transformed IL-6 and NT-proBNP was 0.28 (95% confidence interval [CI] 0.12-0.44, P = 0.001) in univariate logisticregression analysis and 0.09 (95% CI -0.04-0.21, P = 0.176) in the fully adjusted model. This relationship was nonlinear, with a point of 2.7, and the β values (and CIs) for the left (<2.7) and right (≥2.7) sides of the inflection point were -0.06 (95% CI -0.23-0.12,P = 0.534) and 0.77 (95% CI 0.18-1.37,P = 0.016) in the fully adjusted model, respectively. Our results suggest a nonlinear association between IL-6 and NT-proBNP levels. Higher IL-6 levels are associated with NT-proBNP in patients with COVID-19.

The clinical and immunological characteristics of COVID-19 patients with delayed SARS-CoV-2 virus clearance.

The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has posed a great threat to human health. Some severe COVID-19 patients still carried detectable levels of SARS-CoV-2 even after prolonged intensive care unit treatment. However, the immunological features of these COVID-19 patients with delayed virus clearance (CDVC) are still unclear. We retrospectively reviewed the clinical and immunological data of 13 CDVC cases, who were admitted into one hospital in Wuhan from February to April 2020. These data were also compared to those of perished (n = 9) and recovered (n = 52) cases. The expression of the exhaustion marker PD-1 on circulating T cells of these patients was measured by flow cytometry. High levels of serum interleukin-6 (IL-6), IL-1β, IL-8, as well as other inflammatory mediators, were seen in CDVC cases. Severe lymphopenia was observed in CDVC patients with the counts of total lymphocytes (0.9 × 109 /L), CD4+ T cells (0.35 × 109 /L), and CD8+ T cells (0.28 × 109 /L) below their corresponding lower limits of normal range. Similar to the perished group, CDVC cases have higher percentages of CD25+ Foxp3+ regulatory T cells (Treg) in circulation. Moreover, enhanced expression of the exhaustion marker PD-1 on CCR7- CD45RA+ effector, CCR7+ CD45RA- central memory, and CCR7- CD45RA- effector memory CD4+ and CD8+ T cells were also observed in CDVC cases. CDVC patients still have SARS-CoV-2 and these cases manifest with severe clinical symptoms due to persistent inflammation. Augmentation of the frequency of circulating Treg, severe lymphopenia, and functional exhaustion of T cells might lead to inefficient clearance of SARS-CoV-2. Therefore, enhancing lymphocyte counts and reversing T-cell exhaustion might be key methods to boost immune responses and eliminate SARS-CoV-2 in CDVC patients.

Diagnostic Performance of Serum MicroRNAs for ST-Segment Elevation Myocardial Infarction in the Emergency Department.

Prompt diagnosis of ST-segment elevation myocardial infarction (STEMI) is essential for initiating timely treatment. MicroRNAs have recently emerged as biomarkers in cardiovascular diseases. This study aimed to evaluate the discriminatory capacity of serum microRNAs in identifying an ischemic origin in patients presenting with chest discomfort to the Emergency Department. The study included 98 participants (78 with STEMI and 20 with nonischemic chest discomfort). Significant differences in the expression levels of miR-133b, miR-126, and miR-155 (but not miR-1, miR-208, and miR-208b) were observed between groups. miR-133b and miR-155 exhibited 97% and 93% sensitivity in identifying STEMI patients, respectively. miR-126 demonstrated a specificity of 90% in identifying STEMI patients. No significant associations were found between microRNAs and occurrence of major adverse cardiovascular events (MACE). However, patients with MACE had higher levels of interleukin (IL)-15, IL-21, IFN-γ-induced protein-10, and N-terminal pro B-type natriuretic peptide compared to non-MACE patients. Overall, there were significant associations among the expression levels of microRNAs. However, microRNAs did not demonstrate associations with either inflammatory markers or cardiovascular risk scores. This study highlights the potential of microRNAs, particularly miR-133b and miR-126, as diagnostic biomarkers for distinguishing patients with STEMI from those presenting with nonischemic chest discomfort to the Emergency Department.

In Systemic Sclerosis Patients, Peripheral Blood CD21low B Cells and Serum IL-4 and IL-21 Influence Joint Involvement.

Systemic sclerosis (SSc) patients have an increased frequency of CD21low B cells and of serum interleukin-4 (IL-4) and IL-21, each possible markers of joint involvement in inflammatory arthritis. The aim of this study was to investigate the possible influence of CD21low B cells, IL-4, and IL-21 on joint involvement in a cohort of 52 SSc patients. The DAS28-ESR was correlated with CD21low B cells (r = 0.452, p < 0.001), IL-4 (r = 0.478, p < 0.001), and IL-21 (r = 0.415, p < 0.001). SSc patients with a DAS28-ESR > 3.2 had more CD21low B cells (12.65% (IQR: 7.11-13.79) vs. 5.08% (IQR: 3.76-7.45), p < 0.01), higher IL-4 levels (132.98 pg/mL (IQR: 99.12-164.12) vs. 100.80 pg/mL (IQR: 62.78-121.13), p < 0.05), and higher IL-21 levels (200.77 pg/mL (IQR: 130.13-302.41) vs. 98.83 pg/mL (IQR: 35.70-231.55), p < 0.01) than patients with a DAS28-ESR ≤ 3.2. The logistic regression analysis models showed that the DAI (OR: 2.158 (95% CI: 1.120; 4.156), p < 0.05) and CD21low B cells (OR: 1.301 (95% CI: 1.099; 1.540), p < 0.01), the DAI (OR: 2.060 (95% CI: 1.082; 3.919), p < 0.05) and IL-4 level (OR: 1.026 (95% CI: 1.006; 1.045), p < 0.01), and the DAI (OR: 1.743 (95% CI: 1.022; 2.975), p < 0.05) and IL-21 level (OR: 1.006 (95% CI: 1.000; 1.011), p < 0.05) were independently associated with a DAS28-ESR > 3.2. An elevated CD21low B cell percentage, IL-4 level, and IL-21 level was associated with higher articular disease activity in patients, suggesting a possible role in the pathogenesis of SSc joint involvement.

Causal effects of systemic inflammatory regulators on chronic kidney diseases and renal function: a bidirectional Mendelian randomization study.

While targeted systemic inflammatory modulators show promise in preventing chronic kidney disease (CKD) progression, the causal link between specific inflammatory factors and CKD remains uncertain. Using a genome-wide association study of 41 serum cytokines from 8,293 Finnish individuals, we conducted a bidirectional two-sample Mendelian randomization (MR) analysis. In addition, we genetically predicted causal associations between inflammatory factors and 5 phenotypes, including CKD, estimated glomerular filtration rate (eGFR), dialysis, rapid progression of CKD, and rapid decline in eGFR. Inverse variance weighting (IVW) served as the primary MR method, while MR-Egger, weighted median, and MR-pleiotropy residual sum and outlier (MR-PRESSO) were utilized for sensitivity analysis. Cochrane's Q test for heterogeneity. Leave-one-out method ensured stability of MR results, and Bonferroni correction assessed causal relationship strength. Seventeen cytokines were associated with diverse renal outcomes. Among them, after Bonferroni correction test, higher tumor necrosis factor alpha levels were associated with a rapid decrease in eGFR (OR = 1.064, 95% CI 1.028 - 1.103, P = 0.001), higher interleukin-4 levels were associated with an increase in eGFR (β = 0.003, 95% CI 0.001 - 0.005, P = 0.002), and higher growth regulated oncogene alpha (GROα) levels were associated with an increased risk of CKD (OR=1.035, 95% CI 1.012 - 1.058, P = 0.003). In contrast, genetic susceptibility to CKD was associated with an increase in GROa, and a decrease in eGFR may lead to an increase in stem cell factor. We did not find the presence of horizontal pleiotropy during the analysis. We discovered causally related inflammatory factors that contribute to the initiation and progression of CKD at the genetic prediction level.

Investigating the association of physical and psychological problems with the levels of interleukin-1 and -6 in COVID-19 patients.

The COVID-19 virus spreads at a high rate, exerting many physical, mental and psychological effects on patients. Patients with COVID-19 have been reported to have high levels of interleukin 1 and interleukin 6. Therefore, this study was conducted to determine the association of physical, mental, and psychological problems with the levels of interleukin-1 and -6 in COVID-19 patients. This is cross-sectional descriptive-analytical research on 121 COVID-19 patients selected using simple random sampling method. The patients were hospitalized in university hospitals affiliated to Ahvaz Jundishapur University of Medical Sciences and Amir al-Momenin Hospital. Data collection tools included the depression anxiety stress scale (DASS), a demographic questionnaire, and a checklist of physical problems. Blood sampling was also done to perform an ELISA test and measure the level of interleukin-1 and -6. Data were analyzed based on independent t-tests, chi-square, regression, and Pearson's correlation coefficient, using SPSS ver. 22. The average age of the 121 patients participating in this study was 53.31 ± 14.09. A direct and statistically significant correlation was observed between body temperature on the first day and interleukin 1 level. A statistically significant negative correlation was observed between blood oxygen saturation level and interleukin-1 and -6 on the first, third and fifth days. Shortness of breath and coughing had a statistically significant correlation with the level of interleukin 1 on the third and fifth days. A direct and statistically significant correlation was observed between body temperature on the first, third and fifth days and interleukin 6 level. Coughing on the third and fifth days had a statistically significant relationship with interleukin 6 level. No direct and non-significant statistical correlation was found between depression and stress and the serum level of interleukin 1, but a significant correlation was observed between anxiety and serum level of interleukin 1. Finally, the results showed that depression, anxiety and stress had a direct and statistically significant correlation with the serum level of interleukin 6. Given the relationship between interleukin-1 and -6 and most physical and psychological problems, level of the inflammatory biomarkers interleukin-1 and -6 can be used to estimate the severity of physical and psychological symptoms in COVID-19 patients.

Elevated interleukin-10 levels in patients with ocular toxoplasmosis.

In elderly patients, ocular toxoplasmosis is one of the most common etiologies of uveitis, which should be differentially diagnosed from ocular lymphoma, another common pathology of uveitis in older adults. The high level of interleukin (IL)-10 and an IL-10/IL-6 ratio higher than 1 (>1.0) are helpful parameters to diagnose ocular lymphoma. In this study, we used aqueous humor samples to detect 4 cases of ocular toxoplasmosis in patients with high levels of IL-10 and an IL-10/IL-6 ratio higher than 1. Our results show that ocular toxoplasmosis may be associated with increased cytokine levels in aqueous humor.