scholarly journals Functional immunoparalysis characterized by elevated Interleukin-10 and Interleukin-10-to-Lymphocyte Count Ratio is associated with severe disease and poor outcomes in coronavirus disease 2019 (COVID-19)

2020 ◽  
Author(s):  
Brandon Michael Henry ◽  
Stefanie Benoit ◽  
Jens Vikse ◽  
Brandon Berger ◽  
Christina Pulvino ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Lymphocyte Count ◽  
Bacterial Infections ◽  
Severe Disease ◽  
Interleukin 10 ◽  
Lymphocyte Ratio ◽  
Count Ratio ◽  
Unit Increase ◽  
Anti Inflammatory ◽  
Poor Outcomes

Objectives: Severe coronavirus disease 2019 (COVID-19) is associated with a dysregulated immune state, called cytokine storm. While research has focused on the hyperinflammation, little research has been performed on the compensatory anti-inflammatory response which if severe may lead to a state of functional immunoparalysis. The aim of this study was to evaluate the anti-inflammatory response to COVID-19, by assessing interleukin-10 (IL-10) and IL-10/lymphocyte count ratio and their association with patient outcomes. Methods: Adult patients presenting to the emergency department (ED) with laboratory-confirmed COVID-19 were recruited. The primary endpoint was peak COVID-19 severity within 30 days of index ED visit. Additional endpoints included COVID-19 severity at ED disposition, development of severe acute kidney injury (AKI) or secondary bacterial infections. Results: A total of 52 COVID-19 patients were enrolled. IL-10 and IL-10/lymphocyte count were significantly higher in patients with severe disease at both time points (all p<0.05), as well as in those who developed severe AKI and secondary bacterial infection (all p≤0.01). In multivariable analysis, a one-unit increase in IL-10 was associated with 42% increased odds of severe COVID-19 (p=0.031), whilst a one-unit increase IL-10/lymphocyte ratio was also associated with 32% increase in odds of severe COVID-19 (p=0.013). Conclusions: The hyperinflammatory response to COVID-19 is accompanied by a simultaneous anti-inflammatory response, which is associated with poor outcomes and may increase the risk of secondary bacterial infections. IL-10 and IL-10/lymphocyte ratio at ED presentation were independent predictors of COVID-19 severity. Functional immunoparalysis in COVID-19 requires further investigation to enable more precise immunomodulatory therapy against SARS-CoV-2.

scholarly journals The anti-inflammatory cytokine response characterized by elevated interleukin-10 is a stronger predictor of severe disease and poor outcomes than the pro-inflammatory cytokine response in coronavirus disease 2019 (COVID-19)

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Brandon Michael Henry ◽  
Stefanie W. Benoit ◽  
Jens Vikse ◽  
Brandon A. Berger ◽  
Christina Pulvino ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Lymphocyte Count ◽  
Inflammatory Cytokine ◽  
Severe Disease ◽  
Interleukin 10 ◽  
Cytokine Response ◽  
Inflammatory Cytokine Response ◽  
Anti Inflammatory ◽  
Poor Outcomes ◽  
Anti Inflammatory Cytokine

AbstractObjectivesSevere coronavirus disease 2019 (COVID-19) is associated with a dysregulated immune state. While research has focused on the hyperinflammation, little research has been performed on the compensatory anti-inflammatory response. The aim of this study was to evaluate the anti-inflammatory cytokine response to COVID-19, by assessing interleukin-10 (IL-10) and IL-10/lymphocyte count ratio and their association with outcomes.MethodsAdult patients presenting to the emergency department (ED) with laboratory-confirmed COVID-19 were recruited. The primary endpoint was maximum COVID-19 severity within 30 days of index ED visit.ResultsA total of 52 COVID-19 patients were enrolled. IL-10 and IL-10/lymphocyte count were significantly higher in patients with severe disease (p<0.05), as well as in those who developed severe acute kidney injury (AKI) and new positive bacterial cultures (all p≤0.01). In multivariable analysis, a one-unit increase in IL-10 and IL-10/lymphocyte count were associated with 42% (p=0.031) and 32% (p=0.013) increased odds, respectively, of severe COVID-19. When standardized to a one-unit standard deviations scale, an increase in the IL-10 was a stronger predictor of maximum 30-day severity and severe AKI than increases in IL-6 or IL-8.ConclusionsThe hyperinflammatory response to COVID-19 is accompanied by a simultaneous anti-inflammatory response, which is associated with poor outcomes and may increase the risk of new positive bacterial cultures. IL-10 and IL-10/lymphocyte count at ED presentation were independent predictors of COVID-19 severity. Moreover, elevated IL-10 was more strongly associated with outcomes than pro-inflammatory IL-6 or IL-8. The anti-inflammatory response in COVID-19 requires further investigation to enable more precise immunomodulatory therapy against SARS-CoV-2.

scholarly journals CORRELATION OF MONOCYTE COUNT, MLR AND NLCR WITH PRESEPSIN LEVEL IN SIRS (Hubungan Jumlah Monosit, MLR dan NLCR dengan Kadar Presepsin pada SIRS)

2018 ◽  
Vol 22 (3) ◽  
pp. 212
Author(s):  
Nurmalia PS ◽  
N. Suci W ◽  
Imam BW
Keyword(s):  
Systemic Inflammatory Response Syndrome ◽  
Inflammatory Response ◽  
Enzyme Immunoassay ◽  
Lymphocyte Count ◽  
Systemic Inflammatory Response ◽  
Monocyte Count ◽  
Lymphocyte Ratio ◽  
Count Ratio ◽  
Hematology Analyzer ◽  
Chemiluminescent Enzyme Immunoassay

Systemic Inflammatory Response Syndrome (SIRS) mempunyai kebahayaan tinggi terjadi sepsis dan kematian. Nilai jumlahkeseluruhan leukosit merupakan salah satu peramal pasien SIRS dengan bakteriemia. Pemeriksaan jumlah monosit, angka bandinglimfosit Monocyte-Lymphocyte Ratio (MLR), Neutrophil-Lymphocyte Count Ratio (NLCR) dapat diketahui dengan pemeriksaan leukosit.Presepsin telah diteliti untuk mencerminkan kondisi sepsis. Penelitian ini bertujuan untuk mengetahui keberadaan hubungan jumlahmonosit, MLR dan NLCR dengan presepsin di SIRS lewat pembuktian. Ada 34 pasien SIRS di ICU RSUP Dr. Kariadi, diambil secaraberturutan antara selama bulan Januari−Februari 2014. Pemeriksaan darah rutin dengan hematology analyzer. MLR dan NLCR dihitung secara manual. Kadar presepsin ditentukan dengan metode Chemiluminescent Enzyme Immunoassay (CLEIA). Uji kenasabanPearson untuk hubungan MLR dan NLCR dengan presepsin. Uji kenasaban Spearman untuk jumlah monosit dengan presepsin. Kadarpresepsin subjek penelitian 286–15687 pg/mL. Terdapat 23(67,8%) subjek yang mempunyai jumlah monosit dalam rentang nilai rujukan.24(70,6%) dan memiliki jumlah neutrofil absolut lebih besar dari rentang nilai rujukan, sedangkan 21(61,8%) mempunyai jumlahlimfosit absolut dalam rentang nilai rujukan. Hubungan jumlah monosit dengan presepsin mempunyai nilai r= -0,204; p=0,247;yang terkait MLR dengan presepsin r=0,163; p=0,358; sedangkan NLCR dengan presepsin r=0,345; p=0,046. Didasari telitian ini,dapat disimpulkan tidak terdapat hubungan bermakna antara jumlah monosit dan MLR dengan presepsin, selain itu didapatkan pulahubungan positif berarti antara NLCR dan presepsin di SIRS.

Diphenyl diselenide subcutaneous supplementation of dairy sheep: effects on oxidant and antioxidant status, inflammatory response and milk composition

2019 ◽  
Vol 59 (3) ◽  
pp. 461 ◽  
Author(s):  
Angelisa H. Biazus ◽  
Chrystian J. Cazarotto ◽  
Gustavo Machado ◽  
Nathieli B. Bottari ◽  
Mariana S. Alves ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Interleukin 10 ◽  
Milk Composition ◽  
Fat Content ◽  
Control Group ◽  
Lactation Period ◽  
Diphenyl Diselenide ◽  
Dairy Sheep ◽  
Positive Effects ◽  
Anti Inflammatory

Diphenyl diselenide ((PhSe)2) is a organoselenium compound with potent antioxidant properties. Therefore, the aim of the present study was to evaluate whether subcutaneous supplementation of (PhSe)2 in dairy sheep has positive effects on milk composition, as well as on the prevention of oxidative stress and exacerbated inflammatory response. For this, 16 primiparous recently calved sheep were divided into the following two groups, with eight animals in each: Group A, the control group; and Group B, the group subcutaneously supplemented with five doses of (PhSe)2 of 3.0µmol/kg each every 7 days. Blood samples from supplemented animals showed increased concentration of antioxidant enzymes (catalase, superoxide dismutase, glutathione peroxidase and glutathione-S-transferase), and reduced reactive oxygen species and lipid peroxidation, which prevented oxidative damage in the lactation period, as well as increased seric interleukin-10, an anti-inflammatory cytokine. In the sera, supplemented animals showed increased total antioxidant capacity and ferric-reducing ability of plasma compared with the control group. As a consequence, supplemented animals showed increased antioxidant variables, as well as reduced protein oxidation in milk samples. Moreover, milk from supplemented sheep showed a higher fat content, and lower total protein and lactose contents in some periods in the study, than did not-supplemented ewes. Seric concentrations of interleukin-1 were lower on Days 30 and 45 in supplemented animals, as well as the concentrations of tumour necrosis factor α in all periods, than were those in the control group, whereas the interleukin-10 concentrations were higher. Thus, dairy sheep supplementation of (PhSe)2 activated antioxidant and anti-inflammatory responses, and increased milk fat content. Moreover, this protocol increased the antioxidant and, consequently, reduced the oxidant concentration in milk, which is desirable for product quality.

scholarly journals Correlation of Platelet-Lymphocyte Ratio (PLR) as 28-Days Sepsis Mortality Predictor in Intensive Care Unit of RSMH Palembang

2021 ◽  
Vol 1 (2) ◽  
pp. 43-62
Author(s):  
Tiara Santi Rizal ◽  
Fredi Heru Irwanto ◽  
Rizal Zainal ◽  
Mgs Irsan Saleh
Keyword(s):  
Intensive Care Unit ◽  
Intensive Care ◽  
Inflammatory Response ◽  
Sensitivity And Specificity ◽  
Inflammatory Marker ◽  
Sepsis Mortality ◽  
Roc Curve Analysis ◽  
Lymphocyte Ratio ◽  
Morbidity Score ◽  
Anti Inflammatory

Introduction. Inflammatory and anti-inflammatory response are important in pathophysiology and mortality of sepsis. Platelet as first line inflammatory marker was found increasing during early phase of infection. Decrease in lymphocyte was caused by disrupted balance between inflammatory and anti-inflammatory response. Platelet-to- lymphocyte ratio (PLR) is a cheap and accessible biomarker of sepsis mortality. This study aims to find the sensitivity and specificity of PLR as mortality predictor of sepsis in 28 days. Methods. This observational analytic study with retrospective cohort design was conducted to 91 sepsis patients in intensive care unit of Dr. Mohammad Hoesin Palembang Central Hospital between January and December 2019. Samples were secondarily collected from medical record during June-July 2020. Data was analyzed using chi-square test, cog regression test, and ROC curve analysis. Results. The result found 50 patients (54,9%) died in 28 days. Morbidity score (Charlson) was the only statistically significant mortality parameter (p=0,009). The study reported PLR cut-off point of >272,22. The sensitivity and specificity of PLR as 28-days sepsis mortality predictor are 84% and 80,49% respectively. Conclusion. PLR is alternatively reliable mortality predictor in sepsis patient, accounted to its relatively high sensitivity and specificity.

scholarly journals Local and systemic influence of toxic levels of airborne ozone on the inflammatory response in rats

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Małgorzata Chmielewska-Krzesińska ◽  
Krzysztof Wąsowicz
Keyword(s):  
Inflammatory Response ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Interleukin 1 ◽  
Interleukin 10 ◽  
Necrosis Factor Alpha ◽  
Genes Expression ◽  
Factor Alpha ◽  
Anti Inflammatory ◽  
Necrosis Factor

Abstract Introduction Ozone is not harmful itself; however, it directly oxidises biomolecules and produces radical-dependent cytotoxicity. Exposure to ozone is by inhalation and therefore the lungs develop the main anti-inflammatory response, while ozone has an indirect impact on the other organs. This study investigated the local and systemic effects of the ozone-associated inflammatory response. Material and Methods Three groups each of 5 Wistar Han rats aged 6 months were exposed for 2h to airborne ozone at 0.5 ppm and a fourth identical group were unexposed controls. Sacrifice was at 3h after exposure for control rats and one experimental group and at 24 h and 48 h for the others. Lung and liver samples were evaluated for changes in expression of transforming growth factor beta 1, anti-inflammatory interleukin 10, pro-inflammatory tumour necrosis factor alpha and interleukin 1 beta and two nuclear factor kappa-light-chain-enhancer of B cells subunit genes. Total RNA was isolated from the samples in spin columns and cDNA was synthesised in an RT-PCR. Expression levels were compared to those of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and analysed statistically. Results All variables changed non-linearly over time comparing experimental groups to the control. Conspicuous expression changes in the subunit genes and cytokines were observed in both evaluated organs. Conclusion Locally and systemically, inflammation responses to ozone inhalation include regulation of certain genes’ expression. The mechanisms are unalike in lungs and liver but ozone exerts a similar effect in both organs. A broader range of variables influential on ozone response should be studied in the future.

Abstract 620: Angiotensin AT2 Receptor Exerts an Anti-inflammatory Response in Lipopolysaccharide-activated THP-1 Macrophages

Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
Isha S Dhande ◽  
Tahir Hussain
Keyword(s):  
Inflammatory Response ◽  
Interleukin 10 ◽  
Receptor Expression ◽  
Human Macrophage ◽  
No Production ◽  
At2 Receptor ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Pre Treatment ◽  
Lps Activation

Macrophages have been shown to be an important contributor to the pathogenesis of hypertension and stroke. The angiotensin AT2 receptor (AT2R), which is expressed in macrophages, is known to promote vasodialation, natriuresis and lower inflammation. The goal of the present study was to explore the anti-inflammatory role of AT2R stimulation in human macrophage-like THP-1 cells activated by lipopolysaccharide (LPS). Phorbol 12-myristate 13-acetate (PMA) differentiated macrophage-like THP-1 cells were treated with AT2R agonist C21 (1 μmol/L) for 30 minutes prior to activation with LPS (1 μg/ml). Media and cells were collected after 24 hours and were analyzed for levels of pro- and anti-inflammatory cytokines and proteins. Pre-treatment with C21 resulted in a 4-fold increase (104.8±6.1 vs 406.7±52.3) in anti-inflammatory interleukin-10 (IL-10) production and a 5-fold decrease (3560±237 vs 588.8±15.94) in pro-inflammatory tumor necrosis factor-α (TNF-α) levels in the media in response to LPS. Predictably, LPS resulted in a 6-fold up-regulation of iNOS expression which was prevented with C21 pre-treatment. A modest decrease in the anti-inflammatory macrophage mannose receptor C type 2 (MRC2) expression was detected with LPS treatment. AT2R agonist pre-treatment, however, increased this receptor expression by ~70% after LPS activation. C21 alone also resulted in a 20% increase in MRC2 expression compared to untreated controls. The anti-inflammatory effect of AT2R activation was abolished in the presence of neutralizing IL-10 antibody (1 μg/ml), indicating a central role for IL-10 in mediating the beneficial response to C21 in LPS activated macrophages. Further, inhibition of nitric oxide (NO) by L-NAME prior to C21 pre-treatment also prevented the decrease in TNF-α and increase in IL-10 in response to AT2R agonist, which suggests that the anti-inflammatory response to C21 may be mediated via increase in NO production prior to LPS activation of macrophages. In conclusion, AT2R stimulation may potentially suppress the inflammatory response of macrophages to LPS by shifting the balance from pro- to anti-inflammatory cytokine production and may prove to be beneficial in the control of the inflammatory component of stroke and hypertension.

scholarly journals Anti-inflammatory response of IL-4, IL-10 and TGF-β in patients with systemic inflammatory response syndrome

2000 ◽  
Vol 9 (3-4) ◽  
pp. 193-195 ◽  
Author(s):  
Donato Torre ◽  
Roberto Tambini ◽  
Silvana Aristodemo ◽  
Giovanna Gavazzeni ◽  
Antonio Goglio ◽  
...  
Keyword(s):  
Systemic Inflammatory Response Syndrome ◽  
Inflammatory Response ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Serum Levels ◽  
Interleukin 10 ◽  
Systemic Inflammatory Response ◽  
Interleukin 4 ◽  
Significant Difference ◽  
Anti Inflammatory

The systemic inflammatory response syndrome (SIRS) is an inflammatory process seen in association with a large number of clinical infective and noninfective conditions.The aim of this study was to investigate the role of anti-inflammatory cytokines such as interleukin–4 (IL–4), interleukin–10 (IL–10), and transforming growth factor-beta (TGF-beta). Serum levels of IL–4, IL–10 and TGF-β were determined in 45 patients with SIRS: 38 patients had SIRS of infectious origin, whereas seven patients had non-infectious SIRS. Twenty healthy subjects were used as controls.Serum levels of IL–4, IL–10 and TGFg were determined by an immunoenzyme assay. A significant increase of IL–4 was observed in these patients at the time of diagnosis and 5 days later. In contrast, serum levels of IL–10 were not increased at the time of diagnosis, but a slight decrease was noted after 5 days. Serum levels of TGF-β were not increased at time of diagnosis, and a slight increase was observed after 5 days. Serum levels of IL–4 were significantly higher in patients with infectious SIRS at the time of diagnosis, whereas no significant difference between infectious and non-infectious SIRS was noted for serum levels of IL–10 and TGF-β at the time of diagnosis and 5 days later.During SIRS, serum levels of IL–4 were significantly increased with a significant correlation between IL–4 and mortality, and only levels of IL–4 were significantly increased in the SIRS caused by infectious stimuli.

scholarly journals The Correlation of Platelet Lymphocyte Ratio (PLR) as 28 Days Sepsis Mortality Predictor in Intensive Care Unit RSMH Palembang

2020 ◽  
Vol 1 (2) ◽  
pp. 42-62
Author(s):  
Tiara Shanty
Keyword(s):  
Intensive Care Unit ◽  
Intensive Care ◽  
Inflammatory Response ◽  
Sensitivity And Specificity ◽  
Inflammatory Marker ◽  
Sepsis Mortality ◽  
Roc Curve Analysis ◽  
Lymphocyte Ratio ◽  
Morbidity Score ◽  
Anti Inflammatory

Introduction. Inflammatory and anti-inflammatory response are important in pathophysiology and mortality of sepsis. Platelet as first line inflammatory marker was found increasing during early phase of infection. Decrease in lymphocyte was caused by disrupted balance between inflammatory and anti-inflammatory response. Platelet-to-lymphocyte ratio (PLR) is a cheap and accessible biomarker of sepsis mortality. This study aims to find the sensitivity and specificity of PLR as mortality predictor of sepsis in 28 days. Method. This observational analytic study with retrospective cohort design was conducted to 91 sepsis patients in intensive care unit of Dr. Mohammad Hoesin Palembang Central Hospital between January and December 2019. Samples were secondarily collected from medical record during June-July 2020. Data was analyzed using chi-square test, cog regression test, and ROC curve analysis. Results. The result found 50 patients (54,9%) died in 28 days. Morbidity score (Charlson) was the only statistically significant mortality parameter (p=0,009). The study reported PLR cut-off point of >272,22. The sensitivity and specificity of PLR as 28-days sepsis mortality predictor are 84% and 80,49% respectively. Conclusion. PLR is alternatively reliable mortality predictor in sepsis patient, accounted to its relatively high sensitivity and specificity.

scholarly journals COVID-19 IN YOUNG AND MIDDLE-AGED ADULTS. PREDICTORS OF POOR OUTCOME AND CLINICAL DIFFERENCES.

2021 ◽  
Author(s):  
eva tabernero ◽  
Luis Alberto Ruiz ◽  
Pedro Pablo España ◽  
Raul Mendez ◽  
Leyre Serrano ◽  
...  
Keyword(s):  
Heart Disease ◽  
Lymphocyte Count ◽  
Cox Regression ◽  
Severe Disease ◽  
Clinical Manifestations ◽  
Low Oxygen ◽  
Middle Aged ◽  
Poor Outcome ◽  
Poor Outcomes ◽  
Middle Aged Adults

ABSTRACT Young and middle-aged adults are the largest group of patients infected with SARS-CoV-2 and some of them develop severe disease. Objective: To investigate clinical manifestations in adults aged 18-65 years hospitalized for COVID-19 and identify predictors of poor outcome. Secondary objectives: to explore potential differences compared to the disease in elderly patients and the suitability of the commonly used community-acquired pneumonia prognostic scales in younger populations. Methods: Multicenter prospective registry of consecutive patients hospitalized for COVID-19 pneumonia aged 18-65 years between March and May 2020. We considered a composite outcome of “poor outcome” including intensive care unit admission and/or use of noninvasive ventilation, continuous positive airway pressure or high flow nasal cannula oxygen therapies and/or death. Results: We identified 513 patients <65 years of age, from a cohort of 993 patients. 102 had poor outcomes (19.8%) and 3.9% died. 78% and 55% of patients with poor outcomes were classified as low risk based on CURB and PSI scores respectively. A multivariate Cox regression model identified six independent factors associated with poor outcome: heart disease, chest pain, anosmia, low oxygen saturation, high LDH and lymphocyte count <800/mL. Conclusions: COVID-19 in younger patients carries significant morbidity and differs in some respects from this disease the elderly. Baseline heart disease is a relevant risk factor, while anosmia and pleuritic pain are more common and protective. Hypoxemia, LDH and lymphocyte count are predictors of poor outcome. We consider that CURB and PSI scores are not suitable criteria for deciding admission in this population.

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