Higher Interleukin-6 Levels Research Articles

Clinical value of interleukin - 6 as a potential biomarker for bronchogenic carcinoma

Background: Interleukin - 6 is found to be involved in various cancer types but countable studies has investigated its role in cancer lung. Objectives: The purpose of this research was to assess Interleukin-6 levels in bronchoalveolar lavage (BAL) and serum of cases with cancer lung and cases with benign lung conditions, and to determine its diagnostic utility for cancer lung. Subjects and Methods: This prospective interventional analytic study was conducted 40 cases at the Chest Department of Tanta University Hospitals. Cases were divided into two distinct groups: Group 1 comprised twenty individuals with bronchogenic carcinoma, while Group 2 comprised twenty individuals with non-malignant lung illnesses with established causes. All cases received a clinical examination, demographic information, and standard investigations. Using ELISA, the expression of interleukin-6 in BAL and serum was analysed. Results: Interleukin-6 levels were elevated in the BAL and serum of cancer cases versus the control group. Interleukin-6 levels in BAL and serum were positively correlated with advanced clinical stages of cancer lung, as were Interleukin-6 levels in BAL and serum. Conclusions: High BAL Interleukin-6 levels were associated with advanced clinical stage of cancer lung and correlated positively with serum Interleukin-6 levels. BAL Interleukin-6 was determined to be a molecular biomarker for cancer lung diagnosis and prognosis based on its high sensitivity and specificity in detecting lung carcinoma.

A Web-Based Method for the Identification of IL6-Based Immunotoxicity in Vaccine Candidates.

Interleukin 6 (IL6) is a major pro-inflammatory cytokine that plays a pivotal role in both innate and adaptive immune responses. In the past, a number of studies reported that high level of IL6 promotes the proliferation of cancer, autoimmune disorders, and cytokine storm in COVID-19 patients. Thus, it is extremely important to identify and remove the antigenic regions from a therapeutic protein or vaccine candidate that may induce IL6-associated immunotoxicity. In order to overcome this challenge, our group has developed a computational tool, IL6pred, for discovering IL6-inducing peptides in a vaccine candidate. The aim of this chapter is to describe the potential applications and methodology of IL6pred. It sheds light on the prediction, designing, and scanning modules of IL6pred webserver and standalone package ( https://webs.iiitd.edu.in/raghava/il6pred/ ).

Increased blood neutrophil extracellular traps (NETs) associated with early life stress: translational findings in recent-onset schizophrenia and rodent model

Higher levels of interleukin (IL)-6 and elevated neutrophil counts are consistently reported in the blood of patients with schizophrenia. Stressors during childhood and/or adolescence are major socioenvironmental risk factors for schizophrenia and may contribute to immune dysregulation. Previous studies using blood cytokines to stratify patients with schizophrenia suggest that only a subset presents a low-grade inflammatory state. However, these studies have not addressed whether environmental factors such as childhood maltreatment contributed to identifying inflammatory clusters. Moreover, a neutrophil-related mechanism (Neutrophil Extracellular Traps; NETs) central to both the initiation and chronicity of autoimmune and inflammatory diseases has never been investigated in psychiatry. Elevated NETs in schizophrenia may predispose patients to inflammatory and autoimmune diseases resulting in reduced life expectancy. We, therefore, investigated NETs as a novel mechanism and biological target in early schizophrenia and their role together with IL-6 and childhood maltreatment in identifying cluster subgroups. We found increased NETs in the plasma of patients with early schizophrenia (n = 78) compared to both their unaffected siblings (n = 25) and community controls (n = 78), irrespective of sex, body mass index, psychoactive drug use, or tobacco smoking. Increased NETs in patients were unrelated to antipsychotic treatment, which was further tested in vitro using fresh neutrophils. By applying unsupervised two-step clustering analysis, we integrated values of NETs, IL-6, and childhood maltreatment scores. We identified two main clusters; childhood maltreatment scores and NETs were the most important variables contributing to cluster separation (high-CL1 and low-CL2), while IL-6 was the least contributor. Patients allocated in the high-CL1 (61.5%) had significantly higher childhood maltreatment scores, NETs, and IL-6 levels than the remaining groups (patients low-CL2, siblings, and controls high-CL1 and low-CL2). We complemented these findings with a rat model based on stress exposure during adolescence that results in several schizophrenia-like changes in adulthood. We found that adolescent stressed rats had higher NETs and IL-6 levels in serum compared to non-stressed rats with a tendency to produce more NETs from the bone marrow. Altogether, this study brings a novel cellular-based mechanism in schizophrenia that, combined with early-stress, could be useful to identify subgroups for more personalised treatments.

Associations Between Dysfunctional Thoughts, Leisure Activities, and IL-6 in Caregivers of Family Members With Dementia.

Dementia caregiving is associated with negative physical health consequences, including inflammation processes. The objective of this study was to analyze the associations between dysfunctional thoughts, frequency of leisure activities, and interleukin 6 (IL-6) in a sample of dementia family caregivers. One hundred forty dementia caregivers participated in this cross-sectional study. The relationships among caregivers' dysfunctional thoughts, leisure activities, and IL-6 were adjusted for demographic characteristics, stressors, and physical and mental health indicators in a linear regression analysis. Higher levels of dysfunctional thoughts ( t = -2.02, p = .045) were significantly associated with lower frequency of leisure activities. In turn, lower frequency of leisure activities was significantly associated with higher levels of IL-6 ( t = -2.03, p = .045). Dysfunctional thoughts were no longer significantly associated with IL-6 levels when both dysfunctional thoughts and leisure activities were included in the same model ( t = 1.78, p = .076). A significant indirect effect was found for the association between higher levels of dysfunctional thoughts and higher levels of IL-6 (standardized indirect effect = 0.036, bootstrap standard error = 0.026, 95% confidence interval = 0.0001-0.1000) through its association with fewer leisure activities. Our findings suggest that the direct effect of caregivers' dysfunctional thoughts on IL-6 may be mediated by the impact on caregivers' frequency of leisure activities. Results suggest that training caregivers in reducing dysfunctional thoughts to thereby increase leisure activities may be useful in reducing inflammation.

Establishment of quantitative indicators for an efficient treatment on masticatory muscle pain.

Although several studies have investigated effective treatments for masticatory muscle pain (MMP), no unified conclusion has been drawn regarding the effectiveness of these treatments. This study aimed to define quantitative indicators for predicting the outcome of MMP treatment. In total, patients aged 20-70 years were recruited and divided into the MMP (n = 24) and control (n = 36) groups, based on the presence of MMP according to the Diagnostic Criteria for Temporomandibular Disorders. At pretreatment, the MMP group was assessed using quantitative indicators such as subjective pain levels, pain duration, graded chronic pain scale (GCPS), and perceived stress scale (PSS). Salivary alpha-amylase (sAA) and interleukin-6 (IL-6) levels were analyzed. The masticatory muscle palpation score and the range of mouth opening were measured. At posttreatment, subjective pain levels, mouth opening, and treatment/medication duration were examined. The PSS and sAA levels were assessed in the control group. sAA levels in the MMP group were significantly higher than those in the control group (p < .05). The masseter muscle palpation score (MPS) showed a positive correlation with IL-6 levels (ρ = 0.503, p < .05) and a negative correlation with nonsteroidal anti-inflammatory drug (NSAID) treatment period (ρ = -0.462, p < .05). The temporalis muscle palpation score (TPS) was positively correlated with pain duration and GCPS grade (ρ = 0.483, p < .05, and ρ = 0.445, p < .05, respectively). Treatment with NSAIDs was effective in the MMP group with high MPS and IL-6 levels, but not in the MMP group with high TPS, pain duration, and GCPS grade.

C-Reactive Protein, Interleukin-6, Trimethylamine-N-Oxide, Syndecan-1, Nitric Oxide, and Tumor Necrosis Factor Receptor-1 in Heart Failure with Preserved Versus Reduced Ejection Fraction: a Meta-Analysis.

The purpose of this review was to synthesize the evidence on non-traditional biomarkers from proteomic and metabolomic studies that may distinguish heart failure (HF) with preserved ejection fraction (HFpEF) from heart failure with reduced ejection fraction (HFrEF) and non-HF. Understanding the pathophysiology of HFpEF continues to be challenging. A number of inflammatory and metabolic biomarkers that have recently been suggested to be involved include C-reactive protein (CRP), interleukin-6 (IL-6), trimethylamine-N-oxide (TMAO), syndecan-1 (SDC-1), nitric oxide (NO), and tumor necrosis factor receptor-1 (TNFR-1). A systematic search was conducted using Medline, EMBASE, and Web of Science with search terms such as "HFpEF," "metabolomics," and "proteomics," and a meta-analysis was conducted. The results demonstrate significantly higher levels of TMAO, CRP, SDC-1, and IL-6 in HFpEF compared to controls without HF and significantly higher levels of TMAO and CRP in HFrEF compared to controls. The results further suggest that HFpEF might be distinguishable from HFrEF based on higher levels of IL-6 and lower levels of SDC-1 and NO. These data may reflect pathophysiological differences between HFpEF and HFrEF.

Neuro-Behcet's Disease Presenting as a Psuedotumoral Brainstem Mass: A Case Report

Objective Herein, we present a rare and diagnostically challenging case of neuro-Behcet disease (NBD) manifesting as a psuedotumoral brainstem mass. Background Psuedotumoral-NBD as a neurologic manifestation of Behcet's disease is rare. Imaging is characterized by mass-like lesions that enhance with contrast, are hyperintense with T2-weighted and fluid-attenuated inversion recovery (FLAIR) and show restricted diffusion. The differential includes glial lesions, lymphomas, infectious and granulomatous lesions. Design/Methods This is a case study of a 33-year-old male of West-African descent with a history of Behcet's disease. Results A 33-year-old male of West-African descent with a history of Behcet's disease, presented two years after his diagnosis with headaches, low-grade fever, genital ulcerations, and horizontal binocular diplopia. Imaging revealed a large right-sided T2/FLAIR hyperintense abnormality in the medulla with a central area of necrosis. Cerebrospinal fluid revealed lymphocytic-predominant pleocytosis with 11·106 cells/L (reference range 0-5), and high levels of interleukin-6. His vasculitis, infectious, paraneoplastic, flow cytometry, and autoimmune panels were negative. He tested positive for hepatitis-B core antigen, and latent tuberculosis. The etiology for his presentation was believed to be parenchymal NBD and he received a 3-day course of intravenous solumedrol (eventually transitioned to prednisone and azathioprine) with significant improvement. Imaging 1-week post-treatment revealed resolution of enhancement, and at 3 months he had near complete lesion resolution. Conclusions NBD can rarely present with a psuedotumoral presentation, which can cause diagnostic uncertainty. A thorough radiologic/laboratory workup should be conducted to exclude other neurologic diagnoses; however, a high index of suspicion for NBD is required in similar cases and a spectacular response to steroids are invaluable in diagnosis.

High Serum Levels of IL-6 Predict Poor Responses in Patients Treated with Pembrolizumab plus Axitinib for Advanced Renal Cell Carcinoma

Renal cell carcinoma (RCC) is the most common type of kidney malignancy worldwide with Pembrolizumab and axitinib treatment (Pembro/Axi) amongst the most effective first-line immunotherapies for advanced RCC. However, it remains difficult to predict treatment response and early resistance. Therefore, we evaluated whether baseline serum interleukin-6 (IL-6) could be a predictive biomarker. Between November 2019 and December 2021, 58 patients with advanced RCC were enrolled, administered first-line Pembro/Axi, and baseline blood samples were analyzed using flow cytometry. The mean baseline serum IL-6 concentration was 8.6 pg/mL in responders and 84.1 pg/mL in patients with progressive disease. The IL-6 cut-off value was set at 6.5 pg/mL using time-dependent receiver operating characteristic curves, with 37.9% of patients having high baseline serum IL-6 levels and 62.1% having low levels. Objective response rates were 58.3% and 36.4% in low and high IL-6 groups, respectively. Overall survival and progression-free survival were longer in patients with low IL-6 levels than in those with high levels. High IL-6 levels were related to reduced interferon-γ and tumor necrosis factor-α production from CD8+ T cells. Overall, high baseline serum IL-6 levels were associated with worse survival outcomes and reduced T-cell responses in Pembro/Axi-treated advanced RCC patients.

Assessing the variability and the role of inflammatory cytokines and monocyte chemoattractant protein-1 (MCP-1) in predicting stroke among hypertensives: A case-control study.

Atherosclerosis is a complex lipid-driven inflammatory disease in which numerous cell types and inflammatory mediators are involved in the progression of hypertension to stroke. Mediators' markers that could predict the progression of hypertension to stroke are of research importance. We assessed the predictive value of individual and combined cytokines and monocyte chemoattractant protein-1 (MCP-1) among hypertensives with or without stroke. In a case-control study, we enrolled 63 cases with stroke and hypertension (HPT-S), 59 stroke-free hypertensives (HPT), and 53 stroke free normotensives as controls (CS). Sociodemographic data and blood samples were collected for the estimation of Interleukin-10 (IL-10), IL-6, IL-8, IL-1β and monocyte chemoattractant protein-1 (MCP-1) using commercially available ELISA kits from Biobase Biotech, Shanghai, China. The Receiver Operator Characteristics (ROC) analysis was used to calculate diagnostic accuracy for cytokines in predicting stroke among hypertensives. A combined bioscore model of IL-10 and MCP-1 was generated to predict stroke among hypertensives. The multiple logistic regression analysis was used to assess the chances of IL-10 and MCP-1 in predicting stroke among hypertensives. Statistical analyses were performed using R-language. The HPT-S group had significantly higher levels of MCP-1 and IL-10 compared to the HPT and CS groups (p < 0.05). There was no significant difference in IL-1β, IL-8 and IL-6 amongst the three study groups. MCP-1 and IL-10 were predictive of stroke occurrence among hypertensives and were used to develop a bioscore model. An elevated MCP-1 and IL-10 with a bioscore 2 had a predictive accuracy of 0.81, a sensitivity of 0.77 and specificity of 0.84. At a bioscore of 1, the sensitivity and specificity for predicting stroke among hypertensives was 97.0% and 61.0% respectively. In a binary logistic regression, having a bioscore of 1 [aOR = 20.43, 95% CI (2.17-192.62), p = 0.008] or 2 [aOR = 26.00, 95% CI (2.92-231.31), p = 0.003] were significantly associated with stroke occurrence among hypertensives. Higher levels of IL-10 with a concomitant level of MCP-1 could serve as a good predictor of stroke among hypertensives. Subsequently, MCP-1 may prove useful as a therapeutic target for atherosclerosis in hypertensives. Combined bioscore of MCP-1 and IL-10 could serve as a good predictor of stroke among hypertensives.

Interleukin-6, infection and cardiovascular outcomes in acute heart failure: Findings from the EDIFICA registry.

Interleukin-6 (IL-6) is upregulated in response to infectious and inflammatory triggers and independently predicts all-cause mortality in acute heart failure (AHF). However, the association of IL-6 with cardiovascular outcomes and its interplay with C-reactive protein and infection, a major precipitating factor in AHF, remains poorly understood. The association between IL-6 and clinical outcomes (180days) in AHF was evaluated using a cohort of 164 patients from the EDIFICA registry. Median IL-6 levels at admission were 17.4pg/mL. Patients in the higher admission IL-6 tertile presented with lower blood pressure and more congestion, were diagnosed more frequently with infection, and had a longer hospital stay. Higher IL-6 levels were associated with increased risk of HF rehospitalization (hazard ratio per log₂ 3.69, 95% confidence interval (CI) 1.26-10.8, p=.017) and the composite of HF rehospitalization or cardiovascular death (hazard ratio per log₂ 3.50; 95% CI 1.28-9.57; p=.014), independently of major AHF prognosticators, including B-type natriuretic peptide and renal function. However, no independent associations were found for all-cause rehospitalization or mortality. Despite a moderate correlation of IL-6 with C-reactive protein (CRP) levels (R=.51), the latter were not associated with clinical outcomes in this population. IL-6 levels associate with higher rate of cardiovascular events in AHF, independently of classical prognosticators and evidence of infection, outperforming CRP as an inflammatory outcome biomarker.

Importance of IL-6 inhibition in prevention and treatment of antibody-mediated rejection in kidney allografts

Interleukin-6 (IL-6) is a cytokine critical for innate and adaptive immune responses. However, persistent expression of high levels of IL-6 are associated with a number of pathologic conditions including autoimmune diseases and capillary leak syndrome. Importantly, in kidney transplant patients, IL-6 may play a role in mediation of cell-mediated rejection (CMR) and antibody-mediated rejection (AMR). This is likely due to the importance of IL-6 in stimulating B cell responses with pathogenic donor-specific antibody (DSA) generation and stimulation of T effector cell responses while inhibiting T regulatory cells. Data from preliminary clinical trials and clinical observations show that tocilizumab (anti-IL-6R) and clazakizumab (anti-IL-6) may have promise in treatment of CMR, AMR and chronic (cAMR). This has led to a phase 3 placebo, randomized clinical trial of clazakizumab for treatment of cAMR, a condition for which there is currently no treatment. The identification of IL-6 production in vascular endothelia cells after alloimmune activation reveals another potential pathway for vasculitis as endothelia cell IL-6 may stimulate immune cell responses that are potentially inhibitable with anti-IL-6/IL-6R treatment. Importantly, anti-IL-6/IL-6R treatments have shown the ability to induce Treg and Breg cells in vivo which may have potential importance for prevention and treatment of DSA development and allograft rejection.

Selective serotonin reuptake inhibitors: New hope in the fight against COVID-19.

The emerging COVID-19 pandemic led to a dramatic increase in global mortality and morbidity rates. As in most infections, fatal complications of coronavirus affliction are triggered by an untrammeled host inflammatory response. Cytokine storms created by high levels of interleukin and other cytokines elucidate the pathology of severe COVID-19. In this respect, repurposing drugs that are already available and might exhibit anti-inflammatory effects have received significant attention. With the in vitro and clinical investigation of several studies on the effect of antidepressants on COVID-19 prognosis, previous data suggest that selective serotonin reuptake inhibitors (SSRIs) might be the new hope for the early treatment of severely afflicted patients. SSRIs' low cost and availability make them potentially eligible for COVID-19 repurposing. This review summarizes current achievements and literature about the connection between SSRIs administration and COVID-19 prognosis.

The Effect of Carriage of &lt;i&gt;CYP3A5*3&lt;/i&gt; and &lt;i&gt;CYP3A4*22&lt;/i&gt; Polymorphic Variants on the Safety of Remdesivir Therapy in Patients with COVID-19

The aim of the study was to assess the association of polymorphic variants CYP3A5*3 6986 A&gt;G rs776746 and CYP3A4*22 rs35599367 C&gt;T with the safety parameters of remdesivir therapy in patients with COVID-19. Material and methods . The study included 156 patients admitted to the City Clinical Hospital No. 15 of the Moscow Health Department with COVID-19 diagnosis, who received remdesivir as an antiviral drug. The frequency of adverse reactions (bradycardia, dyspeptic disorders), as well as various laboratory parameters (ALT, AST, creatinine, ferritin, interleukin-6, and d-dimer levels) were compared between the carriers of wild-type and polymorphic variants of the studied genes. Results . Carriers of CYP3A5*3 polymorphic variants (GA+AA) had higher ALT levels after the treatment with remdesivir than carriers of the wild variant (GG). When comparing the level of interleukin-6 after therapy with remdesivir, carriers of the polymorphic variant of the CYP3A4*22 (CT) gene had a significantly higher level of this cytokine. Conclusion . An association between the carriage of polymorphic variants of CYP3A5*3 and an increase in the level of liver enzymes was found. Polymorphic variants of CYP3A4*22 were associated with higher levels of interleukin-6. Additional pharmacogenetic studies are required to assess the possibilities of personalizing antiviral therapy for COVID-19.

Immune-Mediated Limbic Encephalitis after Haplo-Identical Hematopoietic Stem Cell Transplantation with Post-Transplant Cyclosphosphamide

Background: Immune-mediated limbic encephalitis (iLE) is a rare, but devastating complication that can develop after allogeneic hematopoietic stem cell transplantation (HSCT). We investigated the biologic characteristics and clinical outcomes of patients with ALE after haploidentical HSCT combined with post-transplant cyclophosphamide (PTCy). Methods: We retrospectively analyzed consecutive adult patients with hematological malignancies who underwent haploidentical HSCT with PTCy at Chungnam National University Hospital between June 2016 and May 2020. ALE was diagnosed by the typical finding of magnetic resonance imaging. We compared the characteristics of patients with and without ALE. Results: Of 35 patients, 4 (11.4%) patients had iLE. The median patient age was 54 years (range, 28-60 years; male : female ratio of 3:1). There were no differences in age, gender, body mass index, hematological disease, conditioning regimen according to iLE status. However, baseline interleukin-6 level before conditioning chemotherapy was higher in patients with iLE than those without iLE [median (range), IL-6; 161.16(103.4 - 199.1) pg/mL vs. 33.78769( 2.1 - 59.1) pg/mL, p < 0.001]. And, Serum IL-6, interferon (IFN)-γ and tumor-necrosis factor (TNF)-α level on day 3 after HSCT was significantly higher in patients with iLE [median (range), IL-6; 355.8 (305.8 - 399.6) pg/mL vs. 63.47 (6.5 - 127.2) pg/mL, p < 0.001/ IFN-γ; 15.045 (6.342 - 29.341) pg/mL vs. 1.602 (0 - 4.036) pg/mL, p = 0.0093 / TNF-α; ; 21.019 (13.268 - 34.138) pg/mL vs. 7.637 (0 - 13.938) pg/mL, p = 0.0205 ]. Patients with iLE had a higher incidence of veno-occlusive disease (VOD) [2 of 4 (50%) vs. 3 of 31 (9.7%), p = 0.030]. The population of naïve regulatory T cells were higher in iLE patient group on day 3 after HSCT than non-iLE group. Overall survival was significantly shorter in patients with iLE [median, 1.5 months, 95% CI, 1.45 - 2.05 vs. 11.0 months, 95% CI, 8.2 - 13.7, p = 0.001]. Conclusion: Patients with high serum interleukin-6 level on baseline & post-transplant day 3, who underwent haploidentical HSCT with PTCy need to be aware of developing iLE.

Association of microalbuminuria with serum lipids and inflammatory markers in an adult population in the Dikgale Health and Demographic Surveillance System site, South Africa.

There is evidence that microalbuminuria (urinary albumin excretion) is an early sign of vascular damage and an established risk factor for cardiovascular morbidity and mortality. This study investigated the magnitude of microalbuminuria and its association with serum lipids and inflammatory markers among a rural black population residing in the Dikgale Health and Demographic Surveillance System site, South Africa. Data were collected from 602 presumably healthy participants (225 men and 377 women) aged ≥ 18 years. Biochemical data collection included serum lipids, glucose, insulin, high-sensitivity C-reactive protein (hs-CRP), urine albumin and creatinine. Anthropometry and blood pressure were also measured. Microalbuminuria was diagnosed with an albumin-creatinine ratio of ≥ 2.5 mg/mmol in men and ≥ 3.5 mg/mmol in women. Data were analysed using SPSS version 22.0. The mean age of participants was 48.63 ± 20.89 years. High percentages of microalbuminaria (35.7%), high levels of interleukin 6 (17.8%), hs-CRP (32.9%), triglycerides (TG) (26.1%), low-density lipoprotein cholesterol (52.2%) and total cholesterol (32.0%), and low levels of high-density lipoprotein cholesterol (29.1%) were observed in the population. Increased glucose levels (32.8%), insulin resistance (27.6%), hypertension (45.8%), overweight (26.8%) and obesity (25.4%) were also prevalent. Microalbuminuria was associated with high hs-CRP and TG levels in the men (adjusted odds ratios = 9.434, 95% confidence interval: 1.753 - 50.778, p = 0.01). High prevalence of microalbuminuria, hypertension, insulin resistance, overweight and obesity, as well as abnormal levels of serum lipids and inflammatory markers were observed in the population. Microalbuminuria was associated with high hs-CRP and TG levels among men.

Immune infiltration in aggressive papillary craniopharyngioma: High infiltration but low action.

Papillary craniopharyngiomas (PCPs) are biologically benign but clinically aggressive lesions hence affect the quality of life. The expression of inflammatory mediators and regulation of the immune microenvironment in PCPs have not been investigated much. In this study, for the first time, we assessed the immune cell infiltration and immune cell signatures in PCPs by analyzing the bulk-RNA sequencing data and immunohistochemical staining. Additionally, we performed qRT-PCR analysis to detect inflammatory mediators interleukin-1α (IL1A) and interleukin-6 (IL6) in different aggressive groups and then developed the IL1A and IL6 prediction models for defining the degree of hypothalamic invasion. Lastly, we defined differentially expressed genes related to invasiveness and implemented enrichment analysis to them. Our results indicated that PCPs are in a state of high immune infiltration but low action with abundant inflammatory cells. High infiltration of neutrophils may lead a low active immune microenvironment. Furthermore, the high expression level of IL1A and IL6 was positively correlated with the invasion of PCP tumors in the hypothalamus. These findings provide new pathological insights into the underlying mechanism of the immune microenvironment in PCP tumors. Moreover, IL1A and IL6 might serve as potential therapeutic targets for PCP tumors, especially to prevent their invasion into the hypothalamus.

Interleukin 6 receptor is not directly involved in regulation of body weight in diet-induced obesity with and without physical exercise.

High level of interleukin 6 (IL-6), released by adipocytes in an obesity-induced, low grade inflammation state, is a regulator of insulin resistance and glucose tolerance. IL-6 has also regenerative, anti-inflammatory and anti-diabetogenic functions, when secreted as myokine by skeletal muscles during physical exercise. IL-6 mainly activates cells via two different receptor constellations: classic and trans-signalling, in which IL-6 initially binds to membrane-bound receptor (IL-6R) or soluble IL-6 receptor (sIL-6R) before activating signal transducing gp130 receptor. Previously, we generated transgenic soluble IL-6 receptor +/+ (sIL-6R+/+) mice with a strategy that mimics ADAM10/17 hyperactivation, reflecting a situation in which only IL-6 trans-signalling is active, whereas classic signalling is completely abrogated. In this study, we metabolically phenotyped IL-6R deficient mice (IL-6R-KO), sIL-6R+/+ mice and wild-type littermates fed either a standard chow (SD) or a high-fat diet (HFD) in combination with a 6-weeks treadmill exercise protocol. All mice were subjected to analyses of body weight and body composition, determination of blood glucose and insulin level under fasting conditions, as well as determination of substrate preference by indirect calorimetry. Neither classic IL-6 nor trans-signalling do influence the outcome of diet-induced obesity, insulin sensitivity and glycaemic control. Furthermore, IL-6R deficiency is not impairing the beneficial effect of physical exercise. We conclude that the IL-6R does not play a requisite role in regulation of body weight and glucose metabolism in diet-induced obese mice.

Predictors of COVID-19 severity among pregnant patients.

Coronavirus disease 2019 (COVID-19) was declared a pandemic and has spread around the globe, unsparingly affecting vulnerable populations. Effective prevention measures for pregnant women, who are particularly affected, include early identification of those patients at risk of developing in-hospital complications, and the continuous improvement of maternal-fetal treatment strategies to ensure the efficient use of health resources. The objective of our retrospective study was to determine which patient biomarkers on hospital admission correlate with disease severity as measured by disease course classification, the need for oxygen supplementation and higher demand for oxygen, the need for mechanical ventilation, intensive care unit admission, and length of hospital stay. Analysis of 52 PCR SARS-CoV-2 positive pregnant women revealed that the median date of hospital admission was the 30th gestational week, with dyspnoea, cough, and fever as the leading symptoms. The presence of diabetes and hypertension predisposed pregnant women to the severe course of illness. Lung involvement shown by CT scans on admission correlated with the greater clinical severity. The main laboratory predictors of disease progression were lymphocytopenia, hypocalcemia, low total cholesterol, low total protein levels, and high serum levels of C-reactive protein, ferritin, interleukin-6, glucose, lactate dehydrogenase, procalcitonin, and troponin I. Further research with a larger cohort of pregnant women is needed to determine the utility of these results for everyday practice.

Interleukin-8 in Colorectal Cancer: A Systematic Review and Meta-Analysis of Its Potential Role as a Prognostic Biomarker.

Among soluble actors that have emerged as druggable factors, the chemokine interleukin-8 (IL-8) has emerged as a possible determinant of response to immunotherapy and targeted treatment in several cancer types; however, its prognostic/predictive role in colorectal cancer (CRC) remains to be established. We: (i) conducted a systematic review of published literature on IL-8 expression in CRC; (ii) searched public transcriptomics databases; (iii) investigated IL-8 expression, by tumor and infiltrating cells, in a series of CRC samples; and (iv) carried out a meta-analysis of published literature correlating IL-8 expression and CRC prognosis. IL-8 possesses an important role as a mediator of the bidirectional crosstalk between tumor/stromal cells. Transcriptomic analysis indicated that specific IL-8 transcripts were significantly overexpressed in CRC compared to normal colon mucosa. Moreover, in our series we observed a statistically significant correlation between PTEN-loss and IL-8 expression by infiltrating mononuclear and tumor cells. In total, 12 papers met our meta-analysis inclusion criteria, demonstrating that high IL-8 levels significantly correlated with shorter overall survival and progression-free survival. Sensitivity analysis demonstrated a highly significant correlation with outcome for circulating, but not for tissue-detected, IL-8. IL-8 is overexpressed in CRC tissues and differentially produced by tumor or stromal components depending on CRC genetic background. Moreover, circulating IL-8 represents a strong prognostic factor in CRC, suggesting its use in the refining of prognostic CRC assessment and potentially the tailoring of therapeutic strategies in individual CRC patients.

Hsa-microRNA-370-3p targeting Snail and Twist1 suppresses IL-8/STAT3-driven hepatocellular carcinoma metastasis.

The pro-inflammatory factor interleukin-8 (IL-8) is related to poor prognosis in hepatocellular carcinoma (HCC) patients. Interleukin-8 enhanced HCC invasion by upregulating Snail and Twist1, whether this modulation relies on microRNAs (miR) is unclear. In this study, hsa-miR-370-3p was screened as candidate miRNA targeting Snail and Twist1, and its expression was downregulated by IL-8. Luciferase assays and RNA electrophoretic mobility shift assays were used to evaluate the interaction between miR-370-3p and targeted mRNAs. Coimmunoprecipitation, luciferase, and ChIP assays were undertaken to investigate the mechanisms underlying IL-8-mediated modification of miR-370-3p. Gain- and loss-of-function studies, Transwell assays, and a xenograft nude mouse model were used to investigate pro- and antitumor activities. Interleukin-8 and miR-370-3p levels were analyzed for clinical relevance in HCC patients. Our results showed that HCC patients with high levels of IL-8 experienced more metastasis and shorter survival. Interleukin-8 induced epithelial-mesenchymal transition and promoted liver cancer cell migration, invasion, and metastasis both in vitro and in vivo. MicroRNA-370-3p interacted with its cognate mRNA within the 3'-UTR regions of Twist1 and Snail mRNA directly and specifically and attenuated IL-8 protumoral effects on liver cancer cells. Interleukin-8 negatively modulated miR-370-3p through signal transducer and activator of transcription 3 (STAT3) activation by recruiting histone deacetylase 1 (HDAC1) to miR-370-3p promoter. The STAT3 and HDAC antagonists inhibited liver cancer cell migration and invasion. Patients with high miR-370-3p and low IL-8 levels had longer overall survival. In conclusion, our study elucidated a novel axis IL-8/STAT3/miR-370-3p/Twist1 and Snail relying on HDAC1 recruitment, which showed both diagnostic and therapeutic potentials of miR-370-3p in HCC metastasis.