Higher Interleukin-6 Research Articles

Inflammation, Lp(a) and cardiovascular mortality: results from the LURIC study.

Lipoprotein(a) [Lp(a)] concentrations have been associated with cardiovascular risk. Recent studies suggested an interaction between systemic inflammation assessed via high-sensitivity C-reactive protein (hsCRP) and Lp(a). This study aimed to evaluate whether Lp(a), hsCRP, and interleukin-6 (IL-6) levels are associated with cardiovascular mortality in a German hospital-based cohort. Data were drawn from the Ludwigshafen Risk and Cardiovascular Health (LURIC) study, including 3,316 patients undergoing coronary angiography. Lp(a) was measured by immunoturbidimetry and categorized into three strata (< 50mg/dL, n = 2668; 50-100mg/dL, n = 482; > 100mg/dL, n = 163). HsCRP was measured by immunonephelometry and categorized by intervals (1st < 1mg/L, 2nd 1-2mg/L and 3rd interval > 2mg/L). IL-6 was measured by ELISA and categorized into two groups (1st < 3.2ng/L, 2nd ≥ 3.2ng/L). The primary outcome was cardiovascular disease (CVD) mortality, analyzed using Cox proportional hazards models and logistic regression. Participants were predominantly male, with a mean age of 62.6years. Extremely high Lp(a) (> 100mg/dL) was associated with increased cardiovascular mortality (HR 1.5, 95% CI 1.06-2.12) compared to Lp(a) < 50mg/dl. Both hsCRP (> 2mg/L, HR 1.39, 95% CI 1.08-1.79 third vs. first interval) and more so IL-6 (HR 1.92, 95% CI 1.64-2.23, upper vs. lower half), were independently associated with higher CVD mortality. While hsCRP did not increase the Lp(a)-CVD mortality in stratified analysis, high IL-6 conferred an increased risk at Lp(a) levels > 100mg/dL (HR 1.25, 95% CI 1.09-1.44). HsCRP and IL-6 are associated with cardiovascular mortality. Markedly elevated Lp(a) is associated with an increased risk of cardiovascular mortality in the context of high systemic inflammation. Anti-inflammatory treatments may provide additional therapeutic benefits for individuals with high Lp(a).

CD4+ T Cells Expressing Viral Proteins Induce HIV-Associated Endothelial Dysfunction and Hypertension Through Interleukin 1α-Mediated Increases in Endothelial NADPH Oxidase 1.

Although combination antiretroviral therapy has increased life expectancy in people living with HIV, it has led to a marked increase in the prevalence of hypertension, the cause of which is unknown. Despite combination antiretroviral therapy, HIV-derived proteins remain expressed and produced by CD4+ T lymphocytes in people living with HIV. However, their contribution to HIV-associated hypertension and impaired endothelium-dependent relaxation remains ill defined. Here, we tested the hypothesis that CD4+ T cells expressing viral proteins contribute to endothelial dysfunction and hypertension using the Tg26 mouse model of HIV that expresses 7 of the 9 HIV proteins under the long terminal repeat promoter. We used male and female mice, bone marrow transplantation (BMT), adoptive transfer of CD4+ T cells, and aorta specimen discarded from people living with HIV. We reported that intact Tg26 mice and mice receiving BMT (Tg26→WT) or CD4+ T cells from Tg26 mice display impaired endothelium-dependent relaxation and hypertension. Conversely, BMT from WT mice into Tg26 mice, inhibition of T cell activation, and CD4+ T cell depletion restored endothelial function and blood pressure in Tg26 mice. Cytokine profiling revealed that Tg26 mice, Tg26→WT, and Tg26 CD4+ T cells consistently exhibit high interleukin 1α (IL-1α) levels with no significant increase in other cytokines, whereas BMT from WT mice into Tg26 mice reduced IL-1α levels. IL-1α neutralization reduced blood pressure and restored endothelial function in Tg26 mice. To investigate the role of CD4+ T cells and IL-1α in endothelial dysfunction, we developed an aorta-immune cell coculture system. Exposure of WT aortas to Tg26 CD4+ T cells impaired endothelium-dependent relaxation, which was blocked by IL-1α-neutralizing antibody. While investigating the mechanisms of endothelial dysfunction, we reported that Tg26 mice, Tg26→WT aorta exhibit high NADPH oxidase (NOX) 1 expression. IL-1α exposure increased NOX1 in human microvascular endothelial cells, and NOX1 blockade restored endothelial function in Tg26 and Tg26→WT arteries, whereas NOX1 deficiency protected against Tg26 BMT-induced impaired endothelium-dependent relaxation and hypertension. Aortas from people living with HIV exhibit high NOX1 levels, and exposure of human aorta to Tg26 T cells increased NOX1 expression. We provide the first evidence that CD4+ T cells expressing HIV viral proteins induced hypertension through IL-1α-mediated increases in vascular NOX1, which impairs endothelial function in males and females.

The dynamics of CD4+ T cell proliferation and regulation

We use mathematical modeling to study the proliferation dynamics of CD4+ T cells within an immune response. This proliferation is driven by the autocrine reaction of helper T cells and interleukin-2 (IL-2), and regulated by natural regulatory T cells (nTregs). Previous studies suggested that a fratricidal mechanism is necessary to eliminate helper T cells post-infection. Contrary to this, our mathematical analysis establishes that the depletion of these cells is due to two pivotal factors: the saturation in the proliferation rate of helper CD4+ T cells at high IL-2 concentrations, and the activation rate of nTregs outpacing their death rate. This yields an excitable process, such that the proliferation starts once the helper T cell population passes a threshold. Additionally, we find that when the proliferation of nTregs lags behind their mortality, induced regulatory T cells (iTregs) are crucial to curbing the proliferation of helper CD4+ T cells.

End-tidal carbon dioxide-guided extracorporeal cardiopulmonary resuscitation improves neurological prognosis in patients: a single-center retrospective cohort study.

Extracorporeal Cardiopulmonary Resuscitation (ECPR) is an effective intervention for restoring adequate circulatory perfusion after cardiac arrest. Ensuring high-quality Cardiopulmonary Resuscitation (CPR) before initiating Extracorporeal Membrane Oxygenation (ECMO) is critical to mitigate tissue hypoxia and ischemia. This study aimed to evaluate the effect of End-Tidal Carbon Dioxide (ETCO2) Goal-Directed CPR (GDCPR) on neurological function before ECMO using a retrospective case-control analysis. The medical records of all patients who received ECPR treated at Zhongshan City People's Hospital were collected between January 2020 and March 2023. In this retrospective cohort study, the patients were divided into Conventional CPR (CCPR) and ETCO2-GDCPR groups based on whether ETCO2 was used as a guide for CPR. A total of 71 patients were included, of whom 46 comprised the CCPR group and 25 comprised the GDCPR group. Approximately 37% of patients who received ECPR had good cerebral function at discharge, with a higher rate in the GDCPR group (52%) compared with the CCPR group (28%) (p = 0.047). Multivariate analysis showed that the Highest Interleukin-6 (H-IL6) levels after ECMO (Odds Ratio [OR = 1.001], 95% Confidence Interval [95% CI 1.000-1.003], p = 0.005) was a risk factor for neurological function at discharge. The other risk factors for poor prognosis in patients who received ECPR included pre-ECMO CPR protocols (OR=10.74, 95% CI 1.90-60.48, p = 0.007) and IL6 levels after ECMO (OR = 1.002, 95% CI 1.001-1.003, p = 0.005). ECMO duration (OR = 0.83, 95% CI 0.74-0.94, p = 0.002) was identified as a protective factor. Patients with short ECMO duration have a poor prognosis. The area under the curve for ECMO duration was 0.86 (0.77-0.94, p < 0.01), while that for H-IL6 was 0.19 (0.09-0.29, p < 0.01). ETCO2-guided ECPR is associated with improved neurological prognosis and patient outcomes. Therefore, monitoring ETCO2 levels should be considered a crucial component of evaluating resuscitation efficacy during CPR.

IL-21 and IL-33 May Be Effective Biomarkers to Predict the Efficacy of PD-1 Monoclonal Antibody for Advanced Cholangiocarcinoma.

Background and Objective: Treatment options for patients with advanced biliary tract cancer (BTC) are limited. The programmed cell death protein-1 (PD-1) inhibitors may have synergistic effects with chemotherapy. Therefore, the aim of our study was to provide real-world data on treatment outcomes in BTC patients receiving chemotherapy alone versus a combination of chemotherapy and PD-1 inhibitors. Additionally, we explored potential markers predictive of PD-1 inhibitor efficacy in this combined therapy. Methods: We conducted a review of patients at Changzhou First People's Hospital who received PD-1 inhibitors in combination with chemotherapy or chemotherapy alone as first-line treatment for advanced BTC. The primary endpoints of the study were progression-free survival (PFS) and overall survival (OS). Kaplan-Meier survival curves and the log-rank test were used to analyze the data. Immunohistochemistry showed the expression of interleukin-21 (IL-21), interleukin-33 (IL-33), and Eomes in the tumor tissue of patients who received PD-1 inhibitors in combination with chemotherapy. Results: The study enrolled 61 patients receiving PD-1 inhibitors combined with chemotherapy and 65 receiving chemotherapy alone. The median OS and PFS for patients receiving PD-1 inhibitors in combination with chemotherapy were 11.7 and 6.7 months, respectively. These durations were significantly longer than those for chemotherapy alone: OS of 10.3 months (95% CI: 0.16-0.21, p = 0.031) and PFS of 5.3 months (95% Confidence interval (CI) 0.25-0.32, p = 0.018). High IL-21 expression or low IL-33 expression in tumor tissue correlated with better response rates to chemotherapy combined with PD-1 inhibitors. Conclusions: Combining PD-1 inhibitors with chemotherapy shows good antitumor activity, making it an effective way to treat BTC. The expression profiles of IL-21 and IL-33 hold promise as potential markers for guiding the chemotherapy combined with immunotherapy in BTC patients.

Anti-TNF nonresponse in ulcerative colitis: correcting for mucosal drug exposure reveals distinct cytokine profiles.

It remains unclear why up to 30% of ulcerative colitis (UC) patients do not respond to tumor necrosis factor inhibitors (TNFi). Validated biomarkers for nonresponse (N)R) are lacking. Most studies investigating underlying mechanisms do not differentiate between pharmacokinetic and inflammatory mechanisms. We therefore aimed to develop a framework to correct for mucosal drug exposure (MDE) and applied this to mucosal cytokine profiles previously linked to (N)R. In a prospective international cohort, we studied patients with active moderate-severe UC starting TNFi treatment. Patients underwent endoscopy before (baseline) and after induction treatment (follow-up). NR was defined as the absence of Mayo endoscopic subscore improvement by central read or need for colectomy. The ratio of mucosal concentrations of TNFi/TNF was used to define high or low MDE. Mucosal concentrations of interleukin-6 (IL-6), Oncostatin M (OSM), interleukin-10 (IL-10), and interleukin-12/23p40 (IL-12/IL-23p40) were measured. Fifty-four UC patients were included (43 infliximab, 11 adalimumab) of whom 39 (72%) were endoscopic responders (after a median treatment of 62 days [48-96]). NR with high MDE had high IL-6 at both time points. R with low MDE exhibited low mucosal IL-10 at baseline. At follow-up, high OSM was associated with NR (irrespective of MDE) and high IL-12/IL-23p40 with R. We incorporated MDE in mucosal cytokine research to avoid bias due to the insufficient presence of anti-TNF. When applied to mucosal cytokines previously linked to (N)R, IL-6 appears to drive inflammation in TNFi-resistant UC patients, while OSM seems to parallel inflammation and does not cause refractoriness.

Elevated Serum IL-6 as a Negative Prognostic Biomarker in Glioblastoma: Integrating Bioinformatics and Clinical Validation.

Background: Glioblastoma multiforme (GBM) is the most lethal type of primary brain tumor, necessitating the discovery of reliable serum prognostic biomarkers. This study aimed to investigate the prognostic value of serum Interleukin-6 (IL-6) in GBM patients. Methods: Bioinformatics analysis via gene set enrichment analysis was conducted on The Cancer Genome Atlas RNA-seq data to explore the pathways enriched in samples with high IL-6 expression. The Tumor IMmune Estimation Resource database was used to analyze the association between IL-6 expression and immune cell infiltration. To validate the role of IL-6 in a clinical setting, a retrospective cohort study was conducted on newly diagnosed GBM patients. Serum IL-6 levels were repeatedly measured at key milestone time points, and their correlation with survival data was analyzed. Results: Bioinformatics analysis revealed that high IL-6 expression is associated with the activation of procancer pathways, that there is a positive correlation between IL-6 expression and immune cell infiltration in GBM. Between March 2021 and September 2023, 36 GBM patients and their serum IL-6 measurements at various time points were included in the clinical data analyses. Elevated serum IL-6 levels at baseline, with a cutoff of 7pg/mL, were identified in 11 patients (30.6%). In the multivariate analyses for overall survival (OS), elevated IL-6 was a significant risk factor (p = 0.048), along with unfavorable surgical resection (p = 0.039) and O6-methylguanine-DNA methyltransferase promotor unmethylation (p = 0.027). The median actuarial OS of the high initial IL-6 group was significantly shorter than that of the low initial IL-6 group (6.4 vs. 19.7 months, p < 0.001). However, IL-6 levels at other time points were not related to patient prognosis. Conclusion: Elevated IL-6 mRNA expression is correlated with the activation of procancer pathways, increased immune cell infiltration, and poor prognosis in GBM patients. In addition, elevated serum IL-6 at baseline is a negative prognostic factor confirmed in a clinical study. Serum IL-6 may be a potential prognostic biomarker enhancing the management of GBM.

High Interleukin (IL)-6 is Associated with Lower Lung Function and Increased Likelihood of Metabolic Dysfunction in Asthma.

Asthma is a complex condition characterized by airway inflammation. Interleukin-6 (IL-6) plays a significant role in asthma pathogenesis through its effects on T cells and its association with pro-inflammatory responses. Both lung and circulating IL-6 levels are elevated in asthma. IL-6 is positively associated with disease severity, frequent exacerbations, and impaired lung function, all of which can be observed clinically. We developed an IL-6 cut-off model to examine the association between high IL-6, race, high body mass index (BMI), metabolic disease, and asthma severity as assessed by reduced lung function. This study utilized the Coronary Artery Risk Development in Young Adults (CARDIA) database, comprised of 5115 adults, to investigate the relationship between IL-6 levels, asthma, race, and metabolic dysfunction. A "healthy" subset of 427 patients was used to compute the IL-6 cut-off. IL-6 levels within detection limits (0.15-12 pg/mL) were analyzed. The IL-6 cut-off was determined using the 95th percentile of log-transformed IL-6 values for lean (BMI<25) and healthy individuals. Specific cut-offs were established for racial groups. Statistical analyses involved comparing patient characteristics between high and low IL-6 groups, regression analyses, and assessment of factors influencing lung function changes. Using an IL-6 cut-off of 4.979 pg/mL, the cohort was divided into high and low IL-6 groups. High IL-6 correlated with Black race, higher BMI, hypertension, and markers of metabolic dysfunction, e.g., elevated HbA1c, C-reactive protein (CRP), and reduced lung function. Multivariable analysis linked high IL-6 with male gender, high BMI, Black race, HbA1c, CRP, and inversely with lung function and total cholesterol. Obesity showed a consistent positive association with elevated IL-6, regardless of the presence or absence of asthma. Patients with asthma and high IL-6 were more likely to be Black and showed increased CRP. Lung function was lowest in non-lean, high IL-6 patients with asthma, with similar trends in non-lean (BMI≥25) patients without asthma. This study underscores the significant association between IL-6, asthma, obesity, and metabolic dysfunction. Elevated IL-6 correlates with asthma severity, particularly in individuals with obesity. Future research should explore anti-IL-6 therapies for specific phenotypes, such as obesity-related asthma. These findings advance our understanding of asthma and the role of IL-6 in its pathogenesis.

Interleukin-6 Modulation in Ovarian Cancer Necessitates a Targeted Strategy: From the Approved to Emerging Therapies.

Despite significant advances in treatments, ovarian cancer (OC) remains one of the most prevalent and lethal gynecological cancers in women. The frequent detection at the advanced stages has contributed to low survival rates, resistance to various treatments, and disease recurrence. Thus, a more effective approach is warranted to combat OC. The cytokine Interleukin-6 (IL6) has been implicated in various stages of OC development. High IL6 levels are also correlated with a lower survival rate in OC patients. In this current review, we summarized the pivotal roles of IL6 in OC, including the initiation, development, invasion, metastasis, and drug resistance mechanisms. This article systematically highlights how targeting IL6 improves OC outcomes by altering various cancer processes and reports the ongoing clinical trials that would further shape the IL6-based targeted therapies. This review also suggests how combining IL6-targeted therapies with other therapeutic strategies could further enhance their efficacy to combat OC.

Elevated IL-6 Expression in Autologous Adipose-Derived Stem Cells Regulates RANKL Mediated Inflammation in Osteoarthritis.

Interleukin-6 (IL-6) expression in mesenchymal stem cells (MSCs) has been shown to play a pivotal role in modulating cartilage regeneration and immune responses, particularly in the context of diseases that involve both degenerative processes and inflammation, such as osteoarthritis (OA). However, the precise mechanism through which IL-6 and other immune-regulatory factors influence the therapeutic efficacy of autologous adipose-derived stem cells (ASCs) transplantation in OA treatment remains to be fully elucidated. This study aims to investigate the relationship between IL-6 expression in autologous ASCs isolated from OA patients and their impact on immune modulation, particularly focusing on the regulation of Receptor Activator of Nuclear factor Kappa-Β Ligand (RANKL), a key mediator of immune-driven cartilage degradation in OA. Autologous ASCs were isolated from the stromal vascular fraction (SVF) of adipose tissue obtained from 22 OA patients. The isolated ASCs were cultured and characterized using reverse transcription polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA), and flow cytometry to the phenotype and immune regulatory factors of MSCs. Based on IL-6 expression levels, ASCs were divided into high and low IL-6 expression groups. These groups were then co-cultured with activated peripheral blood mononuclear cells (PBMCs) to evaluate their immune-modulatory capacity, including the induction of regulatory T cells, inhibition of immune cell proliferation, and regulation of key cytokines, such as interferon-gamma (IFN-γ). Additionally, RANKL expression, a critical factor in osteoclastogenesis and cartilage degradation, was assessed in both ASC groups. High IL-6-expressing ASCs demonstrated a significantly greater capacity to inhibit immune cell proliferation and IFN-γ production compared to their low IL-6-expressing counterparts under co-culture conditions. Moreover, the group of ASCs with high IL-6 expression showed a marked reduction in RANKL expression, suggesting enhanced potential to control osteoclast activity and subsequent cartilage defect in OA. Conclusion: Autologous ASCs with elevated IL-6 expression exhibit enhanced immunomodulatory properties, particularly in regulating over-activated immune response and reducing osteoclastogenesis through RANKL suppression. These findings indicate that selecting ASCs based on IL-6 expression could enhance the therapeutic efficacy of ASC-based treatments for OA by mitigating immune-driven joint inflammation and cartilage degradation, potentially slowing disease progression.

IL-10 EXPRESSION LEVELS AS POTENTIAL BIOMARKER IN WOMEN WITH SLE

Systemic Lupus Erythematosus (SLE) is a multi-systemic autoimmune disease. Its etiology is unclear; however, genetics, environmental, and immunological factors have already been related to the pathogenesis of the disease. There is evidence that cytokines can contribute to SLE, modulating innate and adaptive immune responses. Interleukin-10 (IL-10) is a pleiotropic cytokine previously related to SLE patients and disease activity status. Genetic polymorphisms at the promoter region of IL-10 have been associated with differential protein production, but the findings are conflicting. To assess the potential involvement of polymorphisms -1082 A/G (rs1800896) and -819 A/C (rs1800871) on the susceptibility to disease and clinical features, we identified these variants by TaqMan® SNP assay in a sample of 135 SLE cases and 130 matched controls from an admixed Brazilian population. High IL-10 expression genotypes (-1082 AG or GG) were associated with a protection for SLE (OR 0.317; 95% CI 0.189–0.525; p = 0.001), while no significant results were found for -819 A/C (OR 1.907; 95% CI 0.966–3.921; p = 0.063). Haplotypes of medium or high IL-10 expression were associated with anti-RO positive autoantibodies (p = 0.038), early diagnosis (p = 0.022), and longer fertility time (p = 0.019), possibly predicting a premature but milder disease. These findings indicate that IL-10 polymorphisms influence the susceptibility to SLE in this Brazilian South population and could predict a phenotype characterized by positivity to Anti-RO, premature diagnosis, and longer fertility time.

FC01 Higher IL-10+ T-cell and Treg-cell counts in psoriatic skin are associated with super-response to guselkumab: data from the Phase 3b GUIDE trial

Abstract Interleukin-10 (IL-10) and regulatory T (Treg) cells are immunosuppressive mediators with key roles in autoimmunity. Their increased presence is believed to counter-regulate pathogenic tissue-resident memory (TRM) and T-helper (Th)17 cells in psoriasis. The ongoing randomized, double-blinded, controlled Phase 3b GUIDE trial (NCTO3818035) examines the clinical and immunological impact of an extended guselkumab [an interleukin (IL)-23p19 subunit inhibitor] dosing interval in patients with moderate-to-severe plaque-type psoriasis. Patients who achieved a psoriasis area and severity index (PASI) = 0 at both Week [W]20 and W28 with guselkumab treatment were defined as super-responders (SRes). In this mechanistic substudy of GUIDE, we aimed to determine whether SRes show immunological differences in skin T-cell composition vs. non-SRes, using flow cytometry analysis of non-lesional (at W0) and lesional (at W0, W4, W28 and W68) skin cells taken from 63 patients. At ­baseline, IL-10+ T-cell counts were higher in both non-lesional and lesional skin of SRes vs. non-SRes (with an SRe to non-SRe ratio of 3.1:1 in non-lesional skin, and a 3.0:1 ratio in lesional skin; P &amp;lt; 0.05). This trend was maintained in lesional skin after treatment with guselkumab, with higher IL-10+ T-cell counts observed in SRes than non-SRes at W4 (with an SRe to non-SRe ratio of 4.6:1; P &amp;lt; 0.05) and at W28 (with a ratio of 4.4:1; P &amp;lt; 0.05). Treg-cell (CD4+CD25+FoxP3+) counts were also higher in SRes at W4 and W28 (with an SRe to non-SRe ratio of 3.1:1 at W4, and a ratio of 2.9:1 at W28; P &amp;lt; 0.05). Further analysis of effector T-cell subsets showed that CD8+ TRM and IL-17A+ T-cell counts in lesional skin were reduced by guselkumab up to W68. Normalization of these T-cell populations in lesional skin to non-lesional skin levels appeared to be earlier in SRes (W28) compared with non-SRes (W68). These findings from GUIDE suggest that clinical super-response to guselkumab may be characterized by higher IL-10+ T-cell and Treg-cell counts, and faster normalization of CD8+ TRM and IL-17A+ T-cell counts. Therefore, higher IL-10+ T-cell and Treg-cell counts may act as predictive biomarkers for a better response to guselkumab in patients with moderate-to-severe plaque-type psoriasis.

Correlation between Myeloperoxidase and Interleukin-6 of Patients with Obstructive Sleep Apnea Syndrome in Thi-Qar Governorate

Abstract This research aimed to detect the relationship between Myeloperoxidase (MPO) and Interleukin-6 (IL-6) in patients obstructive sleep apnea syndrome (OSAS). The present study has been conducted on a number of healthy people and patients. Group A: 84 patients Obstructive sleep apnea syndrome (mild, mod and sever) with high blood pressure [47 male, 37 female] and age range (40 - 65). Group B: control group, consist of 64 healthy people [33 male, 31 female] and age range (40 - 65). The findings from the current research indicated a notable rise in levels of serum MPO and serum IL-6 among patient groups when compared with the control group (P≤0.05). Results indicated that there was a positive correlation between MPO with IL-6 in patients with OSAS. OSA patients show high serum myeloperoxidase and serum interleukin-6 concentrations, which signal heightened systemic inflammation and oxidative stress. These factors, part of the pathogenesis of cardiovascular disease are important risk predictors to measure in OSA patients: this can be helpful for early diagnosis of the disease.

A diagnostic index for predicting heart rate variability decline and prognostic value in newly diagnosed non-small cell lung cancer patients.

Heart rate variability (HRV) is an important marker of autonomic nervous system function and cardiovascular health. Holter monitoring is a crucial method for evaluating HRV, but the procedure and result analysis are relatively complex. This study aims to develop a simplified diagnostic index for predicting HRV decline in newly diagnosed non-small cell lung cancer (NSCLC) patients and evaluate its prognostic value. This retrospective cross-sectional study included 131 newly diagnosed NSCLC patients. Baseline characteristics were compared between normal HRV group and declined HRV group. Univariate and multivariate logistic regression analyses identified significant predictors of HRV decline. A diagnostic index was developed based on resting heart rate (RHR), serum sodium, and interleukin-6 (IL-6) and externally validated. Kaplan-Meier survival analysis assessed the prognostic value of the index. Patients with declined HRV had higher median RHR (84 b.p.m. vs. 70 b.p.m., p < 0.001), lower serum sodium (136.3 mmol/L vs. 138.7 mmol/L, p < 0.001), lower serum albumin (39 g/L vs. 41 g/L, p = 0.031), higher lactate dehydrogenase (LDH) (202 U/L vs. 182 U/L, p = 0.010), and higher IL-6 (11.42 pg/ml vs. 5.67 pg/ml, p < 0.001). Multivariate analysis identified RHR (OR = 3.143, p = 0.034), serum sodium (OR = 6.806, p < 0.001), and IL-6 (OR = 3.203, p = 0.033) as independent predictors of HRV decline. The diagnostic index, with an area under the curve (AUC) of 0.849, effectively predicted HRV decline. ROC analysis of the external validation data demonstrated an AUC of 0.788. Survival analysis showed that patients with a diagnostic index > 2 had significantly worse overall survival (log-rank p < 0.001). The study identified key clinical parameters that predict HRV decline in newly diagnosed NSCLC patients. The developed diagnostic index, based on RHR, serum sodium, and IL-6, effectively stratifies patients by HRV status and has significant prognostic value, aiding in early identification and management of high-risk patients.

Immune Profile and MRI-Detected Cardiac Fibrosis and Edema in Hypertensive and Non-Hypertensive Patients with COVID-19.

Cardiac involvement in 2019 coronavirus disease (COVID-19) survivors has been reported frequently. An exacerbated immune response may be the main mechanism of myocardial injury and late cardiac sequelae in this population. Background/Objectives: We investigated the immune profile in hypertensive and non-hypertensive patients with COVID-19 who developed late cardiac fibrosis and edema, as detected by magnetic resonance imaging (MRI). Methods: We evaluated associations of cytokine and immune-cell subset levels during hospitalization for COVID-19 with the presence of myocardial interstitial fibrosis [represented by the extracellular volume (ECV)] or edema (represented by the T2), detected by cardiac MRI examination after discharge, in hypertensive and non-hypertensive patients. Results: Patients with hypertension had reduced B-cell percentages, increased natural killer cell percentages, and higher interleukin (IL)-4, IL-5, IL-13, IL-17A, and tumor necrosis factor-β levels compared to patients without hypertension. Larger percentages of human leukocyte antigen DR isotope+ blood cells, reflecting CD8+ T-cell activation, correlated with increased T2 and ECV in hypertensive patients. The HLA-DR mean fluorescence intensity was associated with ECV in non-hypertensive patients. Conclusions: Our findings reveal cytokine and immune-cell dysregulation in both hypertensive and non-hypertensive patients with COVID-19, along with moderate correlations between CD8+ T-cell activation and increased cardiac MRI markers of myocardial interstitial fibrosis and edema. These results contribute to a deeper understanding of immune dysfunction mechanisms involved in myocardial remodeling.

The proinflammatory status, based on preoperative interleukin-6, predicts postpancreatectomy acute pancreatitis and associated postoperative pancreatic fistula after pancreaticoduodenectomy.

Early predictors of morbidity after pancreaticoduodenectomy (PD) can guide tailored postoperative management. Preoperative inflammatory data in patients who underwent PD remained poorly studied in investigating the clinical significance of predicting postpancreatectomy acute pancreatitis (PPAP) and PPAP-associated postoperative pancreatic fistula (POPF). The clinical data of 467 patients receiving PD between January 2020 and December 2022 were retrospectively reviewed. Preoperative inflammatory data were stratified according to PPAP, and independent risk factors were analyzed. Multivariate logistic regression and subgroup analyses were conducted to compare risk factors of PPAP-associated POPF and non-PPAP-associated POPF. PPAP occurred in 17.6% of patients. The incidence of other complications increased following PPAP. Among the preoperative inflammatory factors, only interleukin-6 (IL-6) increased (P<0.001), leading to a higher incidence of PPAP and POPF (P<0.001; P=0.002). The area under the curve of IL-6 in predicting PPAP was 0.71 (0.65-0.77; P<0.001). Abnormal preoperative IL-6 levels (odds ratio [OR]: 5.01; P<0.001), soft pancreatic texture (OR: 2.15; P=0.007), and pathology (OR: 2.03; P=0.012) were independent risk factors for PPAP. The subgroup analysis showed that increased IL-6 (OR: 1.01; P=0.006) and soft pancreatic texture (OR: 2.05; P=0.033) resulted in a higher risk of PPAP-associated POPF, while increased IL-8 (OR: 1.01; P=0.007), older age (OR: 1.05; P=0.008), and higher body mass index (OR: 1.12; P=0.021) correlated with non-PPAP-associated POPF. PPAP is common after PD; a high preoperative IL-6 level can predict its occurrence, in addition to associated POPF, which could be due to a preoperative proinflammatory status.

CNSC-42. PROGNOSTIC VALUE OF INTERLEUKIN-6 IN PATIENTS WITH GLIOBLASTOMA

Abstract Interleukin-6 (IL-6), a pro-inflammatory cytokine, has been implicated in the invasiveness and progression of glioma. However, the association between serum IL-6 levels at specific time points during treatment and patient prognosis remains unclear. This study was aimed to investigate the prognostic value of IL-6 measured at milestones in the treatment of patients with glioblastoma. Between January 2021 and December 2022, consecutive patients with newly diagnosed glioblastoma were enrolled. Serum IL-6 concentrations were measured at different time points, including preoperative, pre- and post-radiation period, and two-month intervals thereafter. Patients with incomplete data were excluded, and increase of IL-6 values due to the overlapping with systemic infection were also excluded from the analysis. During the study period, 26 patients and 270 IL-6 levels at different time points were evaluated. The median follow-up time was 11 months. Tumor progression was evident in 19 patients (73.1%) and 13 patients (50%) were expired. Preoperative and pre-radiation IL-6 values were available in 20 and 23 patients with the median 5.25 and 4.5 pg/mL, respectively. With the cut-off value of pre-radiation IL-6 at 4.5 pg/mL, high IL-6 group showed significantly worse progression-free survival and overall survival than low IL-6 group (p = 0.027 and 0.008, respectively). However, IL-6 levels at other milestone were not related to the patient prognosis. Serum IL-6 elevation in pre-radiation period is an unfavorable prognostic factor in tumor progression and patient survival. Further research is necessary to validate the prognostic role of IL-6 and explore the underlying mechanisms.

Profile of Cytokines and T Cell Subsets Transcription Factors in Cerebrospinal Fluid of Patients with Viral Encephalitis.

This study investigates the demographic, clinical characteristics, virological profiles, and immunological responses of patients with viral encephalitis (VE) compared with a control group. The VE group displayed a wide range of neurological symptoms. Virological analysis revealed the predominance of Herpesviridae family viruses. Immune responses in cerebrospinal fluid (CSF) from patients with VE were examined, highlighting an immunological shift toward T helper 1 (Th1) cells dominance, altered T helper 17 cells/regulatory T cells (Th17/Tregs) balance, and high interleukin-6 expression. These findings provide insights into the complex immunological landscape of VE, highlighting the role of specific cytokines and T cell subsets in its pathogenesis and potentially guiding targeted therapeutic strategies.

Blood-based inflammatory markers in female infertility: evidence from Mendelian randomization analysis

To investigate causal associations between blood-based inflammatory markers and female infertility using Mendelian randomization (MR). Mendelian randomization using genome-wide association study data. Publicly available genome-wide association study data. Large female-only cohorts of European ancestry. Blood-based inflammatory markers (C-reactive protein, interleukins, monocyte chemoattractant protein-1, tumor necrosis factor-α, interferon-γ). Anovulatory infertility (1,054 cases and 117,098 controls); female infertility of other/unspecified origin (5,667 cases and 117,098 controls); and medical treatment for female infertility (2,706 cases and 120,873 controls). Total causal effects were assessed using univariable two-sample methods including inverse variance weighted (IVW) as the primary analysis, as well as other secondary analyses (MR-Egger, weighted median, etc.), with relevant quality assessments. Interleukin-8 demonstrated a positive association with anovulatory infertility via IVW (odds ratio, 95% confidence interval; 1.51, 1.04-2.21) and weighted median (1.64, 1.05-2.57) methods. Monocyte chemoattractant protein-1 was associated with anovulatory infertility via MR-Egger (2.06, 1.13-3.77). Inverse associations were found for interleukins-12 and -18 via IVW, with higher interleukin-12 being associated with lower medical treatment for female infertility (0.75, 0.59-0.94), whereas higher interleukin-18 was associated with lower female infertility of other/unspecified origin (0.90, 0.83-0.97). This is the first study to examine causal relationships between inflammation and female infertility using MR. Monocyte chemoattractant protein-1 and interleukin-8 are implicated in anovulatory infertility; however, only the relationship with interleukin-8 was evident in the primary analysis. Interleukins-12 and -18 demonstrated inverse associations with infertility outcomes. Further research is needed to uncover the mechanistic functions of these markers to confirm causality and examine their therapeutic potential for female infertility.

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.