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.

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.

Immunoinflammatory Biomarkers in Serum Are Associated with Disease Severity in Atopic Dermatitis

Dermatology ◽  
2021 ◽  
pp. 1-8
Author(s):  
Jesper Grønlund Holm ◽  
Guillem Hurault ◽  
Tove Agner ◽  
Maja Lisa Clausen ◽  
Sanja Kezic ◽  
...  
Keyword(s):  
Atopic Dermatitis ◽  
Disease Severity ◽  
Predictive Models ◽  
Severe Disease ◽  
Serum Levels ◽  
Disease Characteristics ◽  
Immunological Markers ◽  
Chemokine Ligand ◽  
Serum Total Ige ◽  
The Relationship

Background: A growing body of evidence links various biomarkers to atopic dermatitis (AD). Still, little is known about the association of specific biomarkers to disease characteristics and severity in AD. Objective: To explore the relationship between various immunological markers in the serum and disease severity in a hospital cohort of AD patients. Methods: Outpatients with AD referred to the Department of Dermatology, Bispebjerg Hospital, Copenhagen, Denmark, were divided into groups based on disease severity (SCORAD). Serum levels of a preselected panel of immunoinflammatory biomarkers were tested for association with disease characteristics. Two machine learning models were developed to predict SCORAD from the measured biomarkers. Results: A total of 160 patients with AD were included; 53 (33.1%) with mild, 73 (45.6%) with moderate, and 34 (21.3%) with severe disease. Mean age was 29.2 years (range 6–70 years) and 84 (52.5%) were females. Numerous biomarkers showed a statistically significant correlation with SCORAD, with the strongest correlations seen for CCL17/thymus and activation-regulated chemokine (chemokine ligand-17/TARC) and CCL27/cutaneous T cell-attracting-chemokine (CTACK; Spearman R of 0.50 and 0.43, respectively, p < 0.001). Extrinsic AD patients were more likely to have higher mean SCORAD (p < 0.001), CCL17 (p < 0.001), CCL26/eotaxin-3 (p < 0.001), and eosinophil count (p < 0.001) than intrinsic AD patients. Predictive models for SCORAD identified CCL17, CCL27, serum total IgE, IL-33, and IL-5 as the most important predictors for SCORAD, but with weaker associations than single cytokines. Conclusions: Specific immunoinflammatory biomarkers in the serum, mainly of the Th2 pathway, are correlated with disease severity in patients with AD. Predictive models identified biomarkers associated with disease severity but this finding warrants further investigation.

scholarly journals The Interplay between Zinc, Vitamin D and, IL-17 in Patients with Chronic Hepatitis C Liver Disease

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Randa Reda ◽  
Amal A. Abbas ◽  
Mai Mohammed ◽  
Shahira F. El Fedawy ◽  
Hala Ghareeb ◽  
...  
Keyword(s):  
Vitamin D ◽  
Chronic Hepatitis ◽  
Hepatitis C ◽  
Disease Severity ◽  
Chronic Hepatitis C ◽  
Healthy Subjects ◽  
Serum Levels ◽  
Chronic Hepatitis C Virus ◽  
Chronic Hcv

Objectives. To assess zinc (Zn) and vitamin D (Vit. D) status in chronic Hepatitis C virus- (HCV) infected patients and their relationship to interleukin- (IL-) 17 and disease severity and then investigate whether Zn and Vit. D3 modulate IL-17 expression in chronic HCV patients.Methods. Seventy patients and fifty healthy subjects were investigated. Serum levels of Zn, Vit. D, and IL-17 were assessed in the patients group and subgroups. Patients lymphocytes were activatedin vitroin the presence or absence of Zn or Vit. D3 and then intracellular IL-17 production was assessed using flow cytometry.Results. Zn and Vit. D were significantly decreased in HCV patients. Increasing disease severity leads to more reduction in Zn level opposed by increasing IL-17 level. Zn potently reduced IL-17 production in a dose-related fashion; however it did not exert any toxic effects. Although Vit. D apparently increases IL17 expression, it is unclear whether it is due to its toxic effect on cell count or lack of definite association between Vit. D and both IL-17 and disease severity.Conclusions. This study demonstrates that Zn modulates IL-17 expression and provides a rationale for evaluating this compound as a supplementary agent in the treatment of chronic HCV.

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.

Therapy of Myelodysplastic Syndrome (MDS) with Azacitidine Given in Combination with Etanercept: A Phase II Study.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1452-1452 ◽  
Author(s):  
Aaron L. Holsinger ◽  
Aravind Ramakrishnan ◽  
Barry Storer ◽  
Pamela S. Becker ◽  
Stephen Petersdorf ◽  
...  
Keyword(s):  
Myelodysplastic Syndrome ◽  
Phase Ii Study ◽  
Mechanisms Of Action ◽  
Hematological Toxicity ◽  
Tnf Receptor ◽  
Laboratory Studies ◽  
Tnf Α ◽  
Common Grade ◽  
Soluble Tnf Receptor ◽  
Sustained Responses

Abstract The heterogeneity of Myelodysplastic Syndrome (MDS) has spurred interest in combining agents with different mechanisms of action in an attempt to improve the frequency and robustness of responses. Laboratory studies in patients with MDS have shown a shift in the relative levels of TNF-α receptor 1 and 2 in favor of receptor 2 in patients with more advanced MDS. Receptor 2 conveys only proliferative (not apoptotic) signals, and blockade of TNF-α may thus interfere with disease progression, while possibly protecting normal hematopoietic precursors. Therefore, we combined an established regimen of azacitidine with administration of the soluble TNF receptor antagonist etanercept in patients with advanced MDS. Twenty-three patients were treated with azacitidine, 75mg/m2/day for 7 days combined with etanercept, 25mg sc twice a week for two weeks every 28 days. Eighteen patients with MDS (4 RAEB-1, 11 RAEB-2, 1 CMML-1, and 2 CMML-2) have completed at least 3 months of therapy and were considered evaluable. Five of these patients had intermediate-1 risk, seven intermediate-2 and six high risk MDS by IPSS. Using the revised International Working Group (IWG) criteria for MDS, 14 patients (78%) responded: 5 patients (28%) had complete remissions (CR), 8 patients (44%) had partial remissions (PR) and 1 patient (6%) had hematologic improvement of neutrophils. Three patients have been on therapy for two years with sustained responses. Two patients developed pneumonias. The most common grade ¾ adverse events were hematological toxicity (78%). This therapeutic combination may be superior to treatment with azacitidine alone and warrants further study.

Central endothelin ETBreceptors mediate IL-1-dependent fever induced by preformed pyrogenic factor and corticotropin-releasing factor in the rat

2006 ◽  
Vol 290 (1) ◽  
pp. R164-R171 ◽  
Author(s):  
Aline S. C. Fabricio ◽  
Giles A. Rae ◽  
Aleksander R. Zampronio ◽  
Pedro D'Orléans-Juste ◽  
Glória E. P. Souza
Keyword(s):  
Receptor Antagonist ◽  
Corticotropin Releasing Factor ◽  
Tnf Receptor ◽  
Conscious Rats ◽  
Tnf Α ◽  
Soluble Tnf Receptor ◽  
The Brain ◽  
Tnf Receptor I

Blockade of central endothelin ETBreceptors inhibits fever induced by LPS in conscious rats. The contribution of ETBreceptor-mediated mechanisms to fever triggered by intracerebroventricular IL-6, PGE2, PGF2α, corticotropin-releasing factor (CRF), and preformed pyrogenic factor derived from LPS-stimulated macrophages (PFPF) was examined. The influence of natural IL-1 receptor antagonist or soluble TNF receptor I on endothelin (ET)-1-induced fever was also assessed. The selective ETBreceptor antagonist BQ-788 (3 pmol icv) abolished fever induced by intracerebroventricular ET-1 (1 pmol) or PFPF (200 ng) and reduced that caused by ICV CRF (1 nmol) but not by IL-6 (14.6 pmol), PGE2(1.4 nmol), or PGF2α(2 nmol). CRF-induced fever was also attenuated by bosentan (dual ETA/ETBreceptor antagonist; 10 mg/kg iv) but unaffected by BQ-123 (selective ETAreceptor antagonist; 3 pmol icv). α-Helical CRF9–41(dual CRF1/CRF2receptor antagonist; 6.5 nmol icv) attenuated fever induced by CRF but not by ET-1. Human IL-1 receptor antagonist (9.1 pmol) markedly reduced fever to IL-1β (180 fmol) or ET-1 and attenuated that caused by PFPF or CRF. Murine soluble TNF receptor I (23.8 pmol) reduced fever to TNF-α (14.7 pmol) but not to ET-1. The results of the present study suggest that PFPF and CRF recruit the brain ET system to cause ETBreceptor-mediated IL-1-dependent fever.

Serum Levels of IL-17, IL-6, TNF-α and Disease Activity in Patients with Rheumatoid Arthritis

2016 ◽  
Vol 42 (04) ◽  
pp. 323-328 ◽  
Author(s):  
M. Beyazal ◽  
G. Devrimsel ◽  
M. Cüre ◽  
A. Türkyılmaz ◽  
E. Çapkın ◽  
...  
Keyword(s):  
Disease Activity ◽  
Severe Disease ◽  
Serum Levels ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Factor Alpha ◽  
High Level ◽  
Necrosis Factor

Abstract Objective: The aim of this study was to evaluate serum levels of interleukin (IL)-17, IL-6, and tumor necrosis factor alpha (TNF-α) in RA patients and to assess the correlation of these cytokines with clinical and laboratory parameters. Materials and Methods: 48 patients with RA and 35 healthy volunteers were enrolled in the study. Disease activity was determined by disease activity score (DAS28) in patients with RA. Patients with RA were categorized as mild (DAS28≤3.2), moderate (3.2<DAS28≤5.1), and severe (5.1<DAS28) according to DAS28. The serum levels of IL-17, IL-6 and TNF-α cytokines were measured by enzyme-linked immuno sorbent assay. Results: The mean serum IL-17 and TNF-α levels did not differ between RA patients and controls (P>0.05). Serum IL-6 levels were significantly elevated in RA patients compared with controls (P<0.001). The increasing trend in mean serum IL-6 levels across group with mild, moderate, and severe disease activity was significant (P<0.001, respectively). In RA patients, serum IL-6 concentrations were significantly correlated with ESR, CRP, DAS28, and VAS (r=0.371, P=0.009; r=0.519, P<0.001; r=0.536, P<0.001; r=0.539, P<0.001, respectively). Also, Serum IL-17 concentrations demonstrated significant correlations with ESR, CRP, but not DAS28 (r=0.349, P=0.015; r=0.299, P=0.039; r=0.274, P=0.060, respectively). Serum TNF-α showed no significant correlation with disease activity indices. Conclusions: This study showed that patients with RA had significantly increased cytokine level for IL-6, but not IL-17 and TNF-α and high level of serum IL-6 cytokine was associated with disease activity. However, further follow-up studies involving large samples are required to clarify precise role of these cytokines in disease development and progress.

Sign in / Sign up

Export Citation Format

Share Document