scholarly journals Increased serum levels of soluble TNF-α receptor is associated with mortality of ICU COVID-19 patients

2020 ◽  
Author(s):  
Esmaeil Mortaz ◽  
Payam Tabarsi ◽  
Hamidreza Jamaati ◽  
Neda Dalil Roofchayee ◽  
Neda KakaDezfuli ◽  
...  
Keyword(s):  
Serum Levels ◽  
High Serum ◽  
Clinical Feature ◽  
Cytokine Storm ◽  
Tnf Receptor ◽  
Soluble Receptors ◽  
Severity Of Disease ◽  
Tnf Α ◽  
Soluble Tnf Receptor

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes coronavirus disease 2019 (COVID-19) has spread to almost 100 countries, infected over 10M patients and resulted in 505K deaths worldwide as of 30th June 2020. The major clinical feature of severe COVID-19 requiring ventilation is acute Respiratory Distress Syndrome (ARDS) with multi-functional failure as a result of a cytokine storm with increased serum levels of cytokines such as TNF-α and IL-6 being reported. TNF-α levels are increased during the cytokine storm in very ill patients and soluble receptors for IL-6 and IL-2 are present in the blood of COVID-19 patients, Objectives: To elucidate the involvement of serum levels of soluble TNF-Receptor of severe and mild COVID-19 patients to determine for severity of disease. Method: We recruited 16 severe COVID-19 patients in the ICU on ventilator support and 26 milder COVID-19 patients who were hospitalised but not within the intensive care unit (ICU) between March-May 2020 at the Masih Daneshvari Hospital Tehran, Iran. After harvesting of whole blood the serum was isolated and soluble TNF-Receptor levels measured by ELISA. Results: Serum levels of the usually inhibitory soluble TNFα receptor 1 (sTNFaR1) were significantly elevated in severe COVID-19 patients at admission to ICU. High serum levels of sTNFaR1 were associated with mortality of severe COVID-19 patients treated within ICU. Conclusions: This pilot study demonstrates for role of STNF-aR1 receptor in severity of disease. Future studies should examine whether lower levels of systemic sTNFaR1 at admission may indicate a better disease outcome.

scholarly journals Increased Serum Levels of Soluble TNF-α Receptor Is Associated With ICU Mortality in COVID-19 Patients

2021 ◽  
Vol 12 ◽  
Author(s):  
Esmaeil Mortaz ◽  
Payam Tabarsi ◽  
Hamidreza Jamaati ◽  
Neda Dalil Roofchayee ◽  
Neda K. Dezfuli ◽  
...  
Keyword(s):  
Disease Severity ◽  
Healthy Subjects ◽  
Severe Disease ◽  
Serum Levels ◽  
Clinical Feature ◽  
Tnf Receptor ◽  
Icu Patients ◽  
Future Studies ◽  
Tnf Α ◽  
Soluble Tnf Receptor

BackgroundSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes coronavirus disease 2019 (COVID-19) has infected over 112M patients and resulted in almost 2.5M deaths worldwide. The major clinical feature of severe COVID-19 patients requiring ventilation is acute respiratory distress syndrome (ARDS) possibly associated with a cytokine storm.ObjectivesTo elucidate serum levels of TNF-α and soluble TNF-Receptor 1 (sTNFR1) in patients with severe and mild COVID-19 disease as determinants of disease severity.MethodsWe determined serum TNF-α and sTNFR1 concentrations in 46 patients with laboratory-confirmed COVID-19 (17 patients with severe disease within the intensive care unit [ICU] and 29 non-severe, non-ICU patients) and 15 healthy controls upon admission using ELISA. Subjects were recruited between March-May 2020 at the Masih Daneshvari Hospital Tehran, Iran.ResultsSerum levels of sTNFRI were significantly higher in ICU patients (P<0.0001) and non-ICU patients (P=0.0342) compared with healthy subjects. Serum sTNFR1 were significantly higher in ICU patients than in non-ICU patients (P<0.0001). Serum TNF-α levels were greater in ICU and non-ICU patients than in the healthy subjects group (p<0.0001). The sTNFRI concentration in ICU (r=0.79, p=0.0002) and non-ICU (r=0.42, p=0.02) patients positively correlated with age although serum sTNFRI levels in ICU patients were significantly higher than in older healthy subjects. The sTNFRI concentration in ICU patients negatively correlated with ESR.ConclusionsThe study demonstrates higher sTNFRI in ICU patients with severe COVID-19 disease and this be a biomarker of disease severity and mortality. Future studies should examine whether lower levels of systemic sTNFR1 at admission may indicate a better disease outcome.

The potential mechanism of N-acetylcysteine in treating COVID-19

2020 ◽  
Vol 21 ◽  
Author(s):  
Nan Zhou ◽  
Xiaofan Yang ◽  
Aie Huang ◽  
Zhenbing Chen
Keyword(s):  
Acute Respiratory Distress Syndrome ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Distress Syndrome ◽  
Serum Levels ◽  
Antiviral Effect ◽  
Cytokine Storm ◽  
Severe Burns ◽  
Tnf Α

Abstract:: N-Acetylcysteine (NAC) has been proposed and used to treat coronavirus disease 2019 (COVID-19). By reviewing the existing pathological studies of COVID-19, it was found that abundant mucus secretion, formation of a hyaline membrane (supportive of acute respiratory distress syndrome), and interstitial fibrous exudation may be important characteristics of COVID-19 and may be pathological targets of drug therapy. In addition, multiple extrapulmonary organ injuries in COVID-19 may be associated with cytokine storm. NAC is an important antioxidant and anti-inflammatory drug. NAC has been demonstrated to have mucolytic effects in bronchitis, relieve respiratory failure in acute respiratory distress syndrome, and inhibit fibrous exudation in interstitial lung disease in clinical studies. These findings suggest that NAC may have a therapeutic effect on the pathological targets of COVID-19. Furthermore, NAC decreases TNF-α, IL-1β, IL-6, IL-8, IL-10, and IL-17 serum levels in patients with sepsis, severe burns, acute liver failure, or peritoneal dialysis and may also reduce cytokine storm in COVID-19. The antiviral effect of NAC on other respiratory viruses may also benefit COVID-19 patients. Summarizing the potential mechanisms of NAC in treating COVID-19 suggests that the role of NAC in COVID-19 treatment is worthy of further research.

scholarly journals SAT0296 SERUM LEPTIN LEVELS IN SYSTEMIC SCLEROSIS PATIENTS WITH ELECTROCARDIOGRAPHIC ABNORMALITIES

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1093.1-1093
Author(s):  
G. Pellegrino ◽  
K. Stefanantoni ◽  
F. Facioni ◽  
C. Angelelli ◽  
A. Gigante ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Chronic Diseases ◽  
Cardiac Fibrosis ◽  
Serum Levels ◽  
High Serum ◽  
Control Group ◽  
Pathologic Finding ◽  
Serum Leptin ◽  
Ecg Abnormalities

Background:Electrocardiographic (ECG) abnormalities are described in 25-75% Systemic Sclerosis (SSc) cases and they are associated with other systemic manifestations as well as with a worse prognosis. There is an increasing need for clinical and laboratory biomarkers to ameliorate the diagnostic and therapeutic approaches to patients with ECG abnormalities, due to their actual low sensitivity and specificity. Adipokines are circulating proteins that appear dysregulated in SSc and leptin in particular is synthesized in response to inflammatory conditions and seems to play a proinflammatory and pro-fibrotic action in SSc. Interesting, many studies in the last years have underlined its role in the cardiac remodeling mechanisms and in the development of cardiac fibrosis in other chronic diseases.Objectives:Aim of our study is to evaluate the role of leptin in the development of cardiac rhythm disorders (CRD) during SSc. Furthermore, by the analysis of the clinical and demographical parameters of our SSc patients, we tried to define other possible features associated with increased serum leptin concentration.Methods:We included eighty-five SSc patients, fulfilling the 2013 ACR/EULAR classification criteria, attending the Regional Rare Disease Center of Policlinico Umberto I of Rome. Fifty presented significant CRD at non-invasive diagnostic techniques (12 Lead ECG, 24-hour Holter ECG). Demographic, clinical, conventional cardiovascular risk factors were examined; instrumental and laboratory assessments were obtained, together with ECG recordings. Thirty-five SSc patients without pathologic finding at ECG traces, matched for demographic and clinical features, were recruited as the control group. In all cases, after obtaining written informed consent, blood samples were taken to measure serum levels of leptin using an ELISA assay (Life Technologies-Italia).Results:The fifty SSc patients with CRD (mean age 51±15 years; F:M 41:9) had pulmonary fibrosis (PF) in 32 cases (64%) and a BMI >25Kg/m2in 22 (44%) while in the control group of thirty-five SSc patients (mean age 49±16 years; F:M 33:2) PF was found in 15 (43%) and a BMI >25Kg/m2in 9 (35%); We detected significantly higher median values of serum leptin in SSc patients with CRD compared to the control group (12027 pg/ml IQR 12314 versus 6392 pg/ml IQR 7103;p 0,0009). Additionally, SSc patients with a BMI> 25 kg/m2(31 cases) as well as those with PF (47 cases) showed a significantly higher median serum leptin levels compared to those with BMI <25 kg/m2(13161 pg/ml IQR 13610 versus 8187 pg/ml IQR 8255;p 0,0008) and those without PF (11740 pg/ml IQR 11940 versus 7616 pg/ml IQR 7855;p 0,0079).Conclusion:To our knowledge this is the first report on high serum levels of leptin in SSc patients with CRD that also confirms its increase in those cases with a BMI >25 kg/m2and with PF, according to scientific literature data. The role of leptin in the pathogenesis of SSc remains unclear although it is already known its involvement in the development of cardiac fibrosis during other chronic diseases. On the basis of these results we speculate on leptin involvement in the pathogenesis of CRD during SSc, although further studies are needed with larger cohort of patients.References:[1]Vacca A et al. Rheumatology, 2014[2]Tyndall AJ et al. Ann Rheum Dis, 2010[3]Muresan L et al. Iran J Pub Health, 2017[4]Sanna T et al. Indian Pacing Electrophysiol J, 2009[5]Riccieri V et al. Clin Exp Rheumatol, 2011[6]Żółkiewicz J et al. Arch Dermatol Res, 2019[7]Huby AC et al. Circulation, 2015[8]Shulze PC et al. Clin Chim Acta, 2005[9]Van de Hoogen F et al. Arthritis Rheum, 2013[10]Gui X et al. Biochem Biophys Res Commun, 2018Disclosure of Interests:Greta Pellegrino: None declared, Katia Stefanantoni Consultant of: ItalfarmacoBoehringer Ingelheim, Fausta Facioni: None declared, Carlotta Angelelli: None declared, Antonietta Gigante: None declared, Roberto Badagliacca: None declared, Carmine Dario Vizza: None declared, Sergio Morelli: None declared, Edoardo Rosato: None declared, Valeria Riccieri: None declared

scholarly journals Prevotella Induces the Production of Th17 Cells in the Colon of Mice

2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Yuan Huang ◽  
Jinhua Tang ◽  
Zheng Cai ◽  
Keqiang Zhou ◽  
Liang Chang ◽  
...  
Keyword(s):  
Th17 Cells ◽  
Serum Levels ◽  
Immunofluorescence Assay ◽  
Mucosal Inflammation ◽  
Mesenteric Lymph Nodes ◽  
Rdna Sequencing ◽  
Tnf Α ◽  
Intestinal Immune System ◽  
Neomycin Sulfate

Th17-mediated mucosal inflammation is related to increased Prevotella bacterial abundance. The actual involvement of Prevotella in the development and accumulation of intestinal Th17 cells at a steady state, however, remains undefined. Herein, we investigated the role of Prevotella in inducing intestinal Th17 cells in mice. Mice were treated with a combination of broad-spectrum antibiotics (including ampicillin, neomycin sulfate, vancomycin hydrochloride, and metronidazole) in their drinking water for 4 weeks and then gavaged with Prevotella for 4 weeks. After inoculation, 16S rDNA sequencing was used to verify the colonization of Prevotella in the colon of mice. The IL-17A as well as IL-17A-expressing T cells was localized and quantified by an immunofluorescence assay (IFA) of colon sections. Th17 cells in the mesenteric lymph nodes of mice were counted by flow cytometry. Systemic immune response to Prevotella colonization was evaluated based on the serum levels of IL-6, TNF-α, IL-1β, IL-17A, IL-10, IL-4, IFN-γ, and IL-2. Th17-polarizing cytokines (IL-6, TNF-α, IL-1β, and IL-2) induced by Prevotella were evaluated by stimulation of bone marrow-derived dendritic cells (BMDCs). Results revealed that after inoculation, Prevotella successfully colonized the intestine of mice and induced the production and accumulation of colonic Th17 cells in the colon. Moreover, Prevotella elevated some of the Th17-related cytokines in the serum of mice. And Th17-polarizing cytokines (IL-6 and IL-1β) produced by BMDCs were mediated mainly through the interaction between Prevotella and Toll-like receptor 2 (TLR2). In conclusion, our data suggest that Prevotella induces the production of Th17 cells in the colon of mice, thus highlighting the potential role of Prevotella in training the intestinal immune system.

CHANGES THE CYTOKINE PROFILE AND CALCIUM-REGULATING HORMONES IN RHEUMATOID ARTHRITIS

2019 ◽  
Vol 64 (11) ◽  
pp. 673-676
Author(s):  
Asmaya Saftar Huseynova
Keyword(s):  
Rheumatoid Arthritis ◽  
Parathyroid Hormone ◽  
Bone Loss ◽  
Hypovitaminosis D ◽  
Serum Levels ◽  
Control Group ◽  
Tnf Α ◽  
High Production ◽  
Serological Variant

The aim was to study the level of some cytokines (İL-2, İL-6, İL-8 TNFα) and calcium regulating hormones (calcitonin, parathyroid hormone, 25 (OH) D) in the blood of patients with rheumatoid arthritis (RA) depending on rheumatoid factor (RF) and the assessment of the role of the revealed violations in the pathogenesis of bone loss in this pathology. For this purpose, 74 patients with RA (59 women, 15 men) aged from 27 to 71 were examined. On the basis of RF in the blood serum, the patients were divided into 2 groups: seronegative and seropositive RA. The control group included 16 healthy individuals (13 women, 3 men). The results obtained that the serological variant of RA affects the serum levels of proinflammatory cytokines and calcium-regulating hormones: more pronounced changes were found in seropositive RA. The high production of IL-2, IL-6, IL-8, TNF-α and parathyroid hormone detected in both groups of patients undoubtedly contributes to the mechanisms of bone loss in RA. In both groups we detected hypovitaminosis D. This results recommended to use this vitamin in the complex treatment of RA.

scholarly journals Calprotectin in rheumatic diseases

2016 ◽  
Vol 242 (8) ◽  
pp. 859-873 ◽  
Author(s):  
Francesca Ometto ◽  
Lara Friso ◽  
Davide Astorri ◽  
Costantino Botsios ◽  
Bernd Raffeiner ◽  
...  
Keyword(s):  
Rheumatic Diseases ◽  
Potential Role ◽  
Inflammatory Diseases ◽  
Disease Process ◽  
Serum Levels ◽  
Autoimmune Disorders ◽  
High Serum ◽  
Response To Treatment ◽  
Tnf Α ◽  
Activated Monocytes

Calprotectin is a heterodimer formed by two proteins, S100A8 and S100A9, which are mainly produced by activated monocytes and neutrophils in the circulation and in inflamed tissues. The implication of calprotectin in the inflammatory process has already been demonstrated, but its role in the pathogenesis, diagnosis, and monitoring of rheumatic diseases has gained great attention in recent years. Calprotectin, being stable at room temperature, is a candidate biomarker for the follow-up of disease activity in many autoimmune disorders, where it can predict response to treatment or disease relapse. There is evidence that a number of immunomodulators, including TNF-α inhibitors, may reduce calprotectin expression. S100A8 and S100A9 have a potential role as a target of treatment in murine models of autoimmune disorders, since the direct or indirect blockade of these proteins results in amelioration of the disease process. In this review, we will go over the biologic functions of calprotectin which might be involved in the etiology of rheumatic disorders. We will also report evidence of its potential use as a disease biomarker. Impact statement Calprotectin is an acute-phase protein produced by monocytes and neutrophils in the circulation and inflamed tissues. Calprotectin seems to be more sensitive than CRP, being able to detect minimal residual inflammation and is a candidate biomarker in inflammatory diseases. High serum levels are associated with some severe manifestations of rheumatic diseases, such as glomerulonephritis and lung fibrosis. Calprotectin levels in other fluids, such as saliva and synovial fluid, might be helpful in the diagnosis of rheumatic diseases. Of interest is also the potential role of calprotectin as a target of treatment.

scholarly journals An inflammatory cytokine signature helps predict COVID-19 severity and death

2020 ◽  
Author(s):  
Diane Marie Del Valle ◽  
Seunghee Kim-schulze ◽  
Huang Hsin-hui ◽  
Noam D Beckmann ◽  
Sharon Nirenberg ◽  
...  
Keyword(s):  
New York ◽  
Disease Severity ◽  
Cox Regression ◽  
Predictive Biomarkers ◽  
Clinical Information ◽  
Serum Levels ◽  
The United States ◽  
High Serum ◽  
Laboratory Test Results ◽  
Tnf Α

The COVID-19 pandemic caused by infection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has led to more than 100,000 deaths in the United States. Several studies have revealed that the hyper-inflammatory response induced by SARS-CoV-2 is a major cause of disease severity and death in infected patients. However, predictive biomarkers of pathogenic inflammation to help guide targetable immune pathways are critically lacking. We implemented a rapid multiplex cytokine assay to measure serum IL-6, IL-8, TNF-α, and IL-1β in hospitalized COVID-19 patients upon admission to the Mount Sinai Health System in New York. Patients (n=1484) were followed up to 41 days (median 8 days) and clinical information, laboratory test results and patient outcomes were collected. In 244 patients, cytokine measurements were repeated over time, and effect of drugs could be assessed. Kaplan-Meier methods were used to compare survival by cytokine strata, followed by Cox regression models to evaluate the independent predictive value of baseline cytokines. We found that high serum IL-6, IL-8, and TNF-α levels at the time of hospitalization were strong and independent predictors of patient survival. Importantly, when adjusting for disease severity score, common laboratory inflammation markers, hypoxia and other vitals, demographics, and a range of comorbidities, IL-6 and TNF-α serum levels remained independent and significant predictors of disease severity and death. We propose that serum IL-6 and TNF-α levels should be considered in the management and treatment of COVID-19 patients to stratify prospective clinical trials, guide resource allocation and inform therapeutic options. We also propose that patients with high IL-6 and TNF-α levels should be assessed for combinatorial blockade of pathogenic inflammation in this disease.

Increased Level of Soluble Interleukin-2 Receptor in Advanced Solid Tumors: A Preliminary Study

1988 ◽  
Vol 74 (6) ◽  
pp. 633-637 ◽  
Author(s):  
Franco Rovelli ◽  
Paolo Lissoni ◽  
Sergio Crispino ◽  
Sandro Barni ◽  
Gabriele Fumagalli ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Solid Tumors ◽  
Interleukin 2 ◽  
Normal Subjects ◽  
Serum Levels ◽  
High Serum ◽  
Human Solid Tumors ◽  
Soluble Interleukin 2 Receptor ◽  
Preliminary Study

Both activated normal and transformed lymphocytes produce not only cell-associated but also cell-free IL-2R. Evidence of high serum concentrations of IL-2R appears to serve as a tumor marker in patients with lymphomas On the contrary, the role of soluble IL-2R in solid neoplasms has still to be defined. This investigation was carried out to analyze soluble IL-2R production in human solid tumors. The study included 35 patients with solid tumors (12 without and 23 with metastases), 58 healthy subjects and 6 lymphoma patients. Among cancer patients, lung and breast carcinoma were the two most frequent neoplasms. In each subject or patient, serum levels of IL-2R were measured by using an enzyme immunoassay. Moreover, in 14/23 patients with metastatic solid tumors, lymphocyte subpopulations were also evaluated. Serum levels of IL-2R were significantly higher in the cancer patients than in the normal subjects. The patients with metastatic solid tumors showed significantly higher mean levels than those without metastases, and similar to those observed in the lymphoma patients. Finally, there was no correlation between serum levels of IL-2R and the T4/T8 ratio, which was reduced in 5/14 cancer patients. Further studies will be needed to establish if elevated concentrations of IL-2R in the serum can contribute to the immunoincompetence of patients with disseminated solid neoplasms.

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