The association between serum interleukin-1 beta and heparin sulphate in diabetic nephropathy patients

Inflammation is considered an important mechanism in the development of diabetes mellitus (DM) and persists for a long time before the occurrence of diabetic nephropathy (DN). Many studies have demonstrated that a decrease in the endothelial glycocalyx (EG) is negatively correlated with proteinuria. To elucidate whether EG damage induced by inflammasomes in DM patients leads to the occurrence of microalbuminuria (MA) and accelerates the progression of DN, this study screened 300 diagnosed DM patients. Finally, 70 type 2 diabetes patients were invited to participate in this study and were divided into two groups: the T2DM group (patients with normal MA and without diabetic retinopathy, n = 35) and the T2DN group (patients with increased MA and diabetic retinopathy, n = 35). Circulating heparin sulphate (HS, EG biomarkers) and interleukin-1 beta (IL-1β, inflammasome biomarkers) of the patients were measured by ELISA. Laboratory data were measured using routine laboratory methods. Patients in the T2DN group had increased serum HS, increased IL-1β, increased CRP, decreased haemoglobin, and increased neutrophils compared to patients in the T2DM group (all P < 0.05). Increased HS and decreased haemoglobin were independently associated with T2DN patients. ROC curves showed that the AUC of HS for the prediction of T2DN was 0.67 (P < 0.05). The combination of HS and haemoglobin yielded a significant increasement in the AUC (0.75, P < 0.001) with optimal sensitivity (71.2%) and specificity (79%). Furthermore, serum IL-1β was positively correlated with HS and was an independent associated factor of HS in the T2DN group. The relationship between HS and IL-1β was not significant in the T2DM group. Our findings surgessed the inflammasome may be associated with and promote damage to the EG during the disease course of DN that manifests as increased MA.

Is the Success of Cefazolin plus Ertapenem in Methicillin-Susceptible Staphylococcus aureus Bacteremia Based on Release of Interleukin 1-beta?

Cefazolin and ertapenem has been shown to be an effective salvage regimen for refractory methicillin-susceptible Staphylococcus aureus bacteremia. Our findings suggest cefazolin plus ertapenem in vitro stimulates interleukin-1β release from peripheral blood monocytes both with and without S. aureus presence. This IL-1β augmentation was primarily driven by ertapenem. These findings support further exploration of cefazolin plus ertapenem in MSSA bacteremia and may partially explain its marked potency in vivo despite modest synergy in vitro .

Interleukin-1 Beta in Peripheral Blood Mononuclear Cell Lysates as a Longitudinal Biomarker of Response to Antidepressants: A Pilot Study

Interleukin-1 beta (IL1β) is primarily produced by monocytes in the periphery and the brain. Yet, IL1β protein levels have to date been investigated in major depressive disorder (MDD) and antidepressant response using either plasma or serum assays although with contradictory results, while mononuclear cell assays are lacking despite their extensive use in other contexts. In this pilot study, we comparatively assessed IL1β in mononuclear lysates and plasma in depressed MDD patients over treatment and healthy controls (HC). We recruited 31 consecutive adult MDD inpatients and 25 HC matched on age, sex, and BMI. Twenty-six patients completed an 8-week follow-up under treatment. IL1β was measured in both lysates and plasma in patients at baseline (T0) and at study end (T1) as well as in HC. We calculated ΔIL1β(%) for both lysates and plasma as IL1β percent changes from T0 to T1. Seventeen patients (65.4% of completers) were responders at T1 and had lower baseline BMI than non-responders (p = 0.029). Baseline IL1β from either plasma or lysates could not efficiently discriminate between depressed patients and HC, or between responders and non-responders. However, the two response groups displayed contrasting IL1β trajectories in lysates but not in plasma assays (response group by time interactions, p = 0.005 and 0.96, respectively). ΔIL1β(%) in lysates predicted response (p = 0.025, AUC = 0.81; accuracy = 84.6%) outperforming ΔIL1β(%) in plasma (p = 0.77, AUC=0.52) and was robust to adjusting for BMI. In conclusion, ΔIL1β(%) in mononuclear lysates may be a longitudinal biomarker of antidepressant response, potentially helpful in avoiding untimely switching of antidepressants, thereby warranting further investigation.

Evaluation of Salivary Interleukin-1 Beta in Covid Recovered Patients

Introduction: The COVID-19 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The epidemic started in Wuhan in mid-December 2019 and quickly spread across the world as a pandemic. Saliva is emerging as a promising alternative to nasopharyngeal/oropharyngeal swabs for COVID-19 diagnosis and monitoring. Aim: To evaluate the Interleukin-1 Beta in the salivary samples of COVID-recovered patients and healthy controls. Materials and Methods: An observational study on saliva samples of COVID recovered patients. The study was non-invasive and easy to perform without much inconvenience to patients. The samples were obtained from patients who came to the clinics of Saveetha Dental College and Hospitals. A total of 20 saliva samples were collected from recruited patients 10 of whom were healthy controls and 10 were collected from patients who had made complete recovery from covid infection at least three months ago Student T test were performed using Statistical Package for the Social Sciences (IBM SPSS statistics for windows version 23.0, Armonk, NY: IBM Corp. Released 2015). Values were expressed as Mean and SD. An observational study on saliva samples of COVID recovered patients.The salivary Interleukin-1 levels were analyzed using ELISA. Results: Within the limitations of the study, we conclude that salivary Interleukin-1 level is increased in COVID recovered patients. The difference was statistically significant proving that in spite of complete uneventful recovery from COVID infection the individual’s inflammatory markers are seen to be at our rise. Conclusion: Salivary Interleukin-1 levels are increased in COVID recovered patients. Further prospective studies with the limited sample size of the salivary levels of IL-1 can effectively assess disease severity and predict outcome in patients with COVID-19.This study illustrates the group of healthy controls and COVID recovered patients.

Comparative analysis of IL-1β blood serum concentration, neutrophil-to-lymphocytes ratio in peripheral blood, and the levels of PD-L1 expression in malignant tissues of the patients with various solid tumors

The action of checkpoint inhibitors is based on activation of T cell antitumor immunity, and, therefore, the search for markers of lymphocyte functional activity before starting the therapy is highly relevant. Determination of the PD-L1 expression in tumor tissues reflects immunosuppressive activity of malignant cells, and it is used as a predictive marker in clinical practice. The ratio of neutrophils to lymphocytes in tumor tissue and in peripheral blood can also indicate the activity of adaptive immunity and correlates with the efficacy of therapy. It has been shown that a high level of interleukin 1 beta in the tumor microenvironment is associated with immunosuppression of lymphocytes and, possibly, reflects the activity of the tumor microenvironment. The aim of this work is to study the relationship between tumor expression of PD-L1, the concentration of serum interleukin-1 beta and the ratio of neutrophils and lymphocytes in peripheral blood.Before starting therapy with checkpoint inhibitors in patients with various solid tumors (n = 50), the serum level of interleukin-1 beta was determined by ELISA (ELISA-Best, Novosibirsk, Russia), expression of PD-L1 in the tumor by immunohistochemical method, complete blood count was performed using cytometry. Statistical analysis was performed in GraphPad Prism 6 (Graph Pad Software, USA) using the statistical methods of Fisher, Mann-Whitney, and Spearman.The average value of the index of the ratio of neutrophils and lymphocytes (NLR) in peripheral blood was 2.65± 0.21 (95% CI 2.22-3.07). The index value of more than 3.5 was found in 18% (9/50) of patients. The mean value of the PD-L1 expression level was 23.02±4.52% (95% CI 13.86-32.18). Expression of PD-L1 in tumor tissue was detected in 60.1% (25/40) of patients, among whom an increased expression of more than 50% was detected in 20.0% (5/25) of cases. A positive weak correlation was found between the concentration of interleukin 1 beta and the number of leukocytes (r = 0.34; p = 0.019) and index (r = 0.32; p = 0.029). The level of PD-L1 expression in tumor tissue also had a weak positive correlation with the serum interleukin 1 beta concentration (r = 0.33; p = 0.037) and the neutrophil-lymphocyte ratio (r = 0.33; p = 0.034). In the group of patients with PD-L1 expression > 5%, the mean value of the concentration of interleukin 1 beta was 1.65±0.62 pg/ml, and the mean value of the index was 4.26±0.94 х 10 9/l, which exceeds the values groups with undetectable PD-L1, but the differences were not statistically significant.The obtained result may indicate the influence of the immunosuppressive properties of the tumor on the state of the patient's immunity. Comprehensive determination of tumor PD-L1 expression, serum interleukin 1 beta concentration and the ratio of neutrophils and lymphocytes in peripheral blood can be used as an assessment of the patient's immune status before starting treatment with checkpoint inhibitors.

Multi-ethnic Investigation of Risk and Immune Determinants of COVID-19 Outcomes

Objectives: To compare risk factors for COVID-19 mortality among hospitalized Hispanic, Non-Hispanic Black, and White patients. Design: Retrospecitve cohort study Setting: Five hosptials within a single academic health system Participants: 3,086 adult patients with self-reported race/ethnicity information presenting to the emergency department and hospitalized with COVID-19 up to April 13, 2020. Main outcome measures: In-hospital mortality Results: While older age (multivariable OR 1.06, 95% CI 1.05-1.07) and baseline hypoxia (multivariable OR 2.71, 95% CI 2.17-3.36) were associated with increased mortality overall and across all races/ethnicities, Non-Hispanic Black (median age 67, IQR 58-76) and Hispanic (median age 63, IQR 50-74) patients were younger and had different comorbidity profiles compared to Non-Hispanic White patients (median age 73, IQR 62-84; p<0.05 for both comparisons). Among inflammatory markers associated with COVID-19 mortality, there was a significant interaction between the Non-Hispanic Black population and interleukin-1-beta (interaction p-value 0.04). Conclusions: This analysis of a multi-ethnic cohort highlights the need for inclusion and consideration of diverse popualtions in ongoing COVID-19 trials targeting inflammatory cytokines.

Knee Osteoarthritis Progression Is Delayed in Silent Information Regulator 2 Ortholog 1 Knock-in Mice

Overexpression of silent information regulator 2 ortholog 1 (SIRT1) is associated with beneficial roles in aging-related diseases; however, the effects of SIRT1 overexpression on osteoarthritis (OA) progression have not yet been studied. The aim of this study was to investigate OA progression in SIRT1-KI mice using a mouse OA model. OA was induced via destabilization of the medial meniscus using 12-week-old SIRT1-KI and wild type (control) mice. OA progression was evaluated histologically based on the Osteoarthritis Research Society International (OARSI) score at 4, 8, 12, and 16 weeks after surgery. The production of SIRT1, type II collagen, MMP-13, ADAMTS-5, cleaved caspase 3, Poly (ADP-ribose) polymerase (PARP) p85, acetylated NF-κB p65, interleukin 1 beta (IL-1β), and IL-6 was examined via immunostaining. The OARSI scores were significantly lower in SIRT1-KI mice than those in control mice at 8, 12, and 16 weeks after surgery. The proportion of SIRT1 and type II collagen-positive-chondrocytes was significantly higher in SIRT1-KI mice than that in control mice. Moreover, the proportion of MMP-13-, ADAMTS-5-, cleaved caspase 3-, PARP p85-, acetylated NF-κB p65-, IL-1β-, and IL-6-positive chondrocytes was significantly lower in SIRT1-KI mice than that in control mice. The mechanically induced OA progression was delayed in SIRT1-KI mice compared to that in control mice. Therefore, overexpression of SIRT1 may represent a mechanism for delaying OA progression.