scholarly journals Serial measurement of cytokines strongly predict COVID-19 outcome

PLoS ONE ◽  
2021 ◽  
Vol 16 (12) ◽  
pp. e0260623
Author(s):  
Hasan Selcuk Ozger ◽  
Resul Karakus ◽  
Elif Nazli Kuscu ◽  
Umit Emin Bagriacik ◽  
Nihan Oruklu ◽  
...  

Purpose Cytokines are major mediators of COVID-19 pathogenesis and several of them are already being regarded as predictive markers for the clinical course and outcome of COVID-19 cases. A major pitfall of many COVID-19 cytokine studies is the lack of a benchmark sampling timing. Since cytokines and their relative change during an infectious disease course is quite dynamic, we evaluated the predictive value of serially measured cytokines for COVID-19 cases. Methods In this single-center, prospective study, a broad spectrum of cytokines were determined by multiplex ELISA assay in samples collected at admission and at the third day of hospitalization. Appropriateness of cytokine levels in predicting mortality were assessed by receiver-operating characteristic (ROC) analyses for both sampling times in paralel to conventional biomarkers. Results At both sampling points, higher levels of IL-6, IL-7, IL-10, IL-15, IL-27 IP-10, MCP-1, and GCSF were found to be more predictive for mortality (p<0.05). Some of these cytokines, such as IL-6, IL-10, IL-7 and GCSF, had higher sensitivity and specificity in predicting mortality. AUC values of IL-6, IL-10, IL-7 and GCSF were 0.85 (0.65 to 0.92), 0.88 (0.73 to 0.96), 0.80 (0.63 to 0.91) and 0.86 (0.70 to 0.95), respectively at hospital admission. Compared to hospital admission, on the 3rd day of hospitalization serum levels of IL-6 and, IL-10 decreased significantly in the survivor group, unlike the non-survivor group (IL-6, p = 0.015, and IL-10, p = 0.016). Conclusion Our study results suggest that single-sample-based cytokine analyzes can be misleading and that cytokine levels measured serially at different sampling times provide a more precise and accurate estimate for the outcome of COVID-19 patients.

2020 ◽  
Vol 8 (3) ◽  
pp. 103-112
Author(s):  
Atefeh SADEGHI SHERMEH ◽  
Majid KHOSHMIRSAFA ◽  
Ali-Akbar DELBANDI ◽  
Payam TABARSI ◽  
Esmaeil MORTAZ ◽  
...  

Introduction: Tuberculosis (TB) and especially resistant forms of it have a substantial economic burden on the community health system for diagnosis and treatment each year. Thus, investigation of this field is a priority for the world health organization (WHO). Cytokines play important roles in the relationship between the immune system and tuberculosis. Genetic variations especially single nucleotide polymorphisms (SNPs) impact cytokine levels and function against TB. Material and Methods: In this research SNPs in IFN-γ (+874 T/A) and IL-10 (-592 A/C) genes, and the effects of these SNPs on cytokine levels in a total of 87 tuberculosis patients and 100 healthy controls (HCs) were studied. TB patients divided into two groups: 1) 67 drug-sensitive (DS-TB) and 2) 20 drug-resistant (DR-TB) according to drug sensitivity test using polymerase chain reaction (PCR). For the genotyping of two SNPs, the PCR-based method was used and IFN-γ and IL-10 levels were measured by ELISA in pulmonary tuberculosis (PTB) and control group. Results: In -592A/C SNP, only two genotypes (AA, AC) were observed and both genotypes showed statistically significant differences between DR-TB and HCs (p=0.011). IL-10 serum levels in PTB patients were higher than HCs (p=0.02). The serum levels of IFN-γ were significantly higher in DS-TB patients than that of the other two groups (p<0.001); however, no significant differences were observed for allele and genotype frequencies in IFN-γ +874. Conclusions: Our results suggest that the SNP at -592 position of IL-10 gene may be associated with the susceptibility to DR-TB. However, further investigation is necessary. Keywords: Polymorphism, IFN-γ, IL-10, tuberculosis, drug-resistant tuberculosis


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Junkun Liu ◽  
Chengwen Bai ◽  
Binbin Li ◽  
Aijun Shan ◽  
Fei Shi ◽  
...  

AbstractEarly identification of infection severity and organ dysfunction is crucial in improving outcomes of patients with sepsis. We aimed to develop a new combination of blood-based biomarkers that can early predict 28-day mortality in patients with sepsis or septic shock. We enrolled 66 patients with sepsis or septic shock and compared 14 blood-based biomarkers in the first 24 h after ICU admission. The serum levels of interleukin-6 (IL-6) (median 217.6 vs. 4809.0 pg/ml, P = 0.001), lactate (median 2.4 vs. 6.3 mmol/L, P = 0.014), N-terminal prohormone of brain natriuretic peptide (NT-proBNP) (median 1596.5 vs. 32,905.3 ng/ml, P < 0.001), prothrombin time (PT) (median 15.6 vs. 20.1 s, P = 0.030), activated partial thrombin time (APTT) (median 45.1 vs. 59.0 s, P = 0.026), and international normalized ratio (INR) (median 1.3 vs. 1.8, P < 0.001) were significantly lower in the survivor group. IL-6, NT-proBNP, and INR provided the best individual performance in predicting 28-day mortality of patients with sepsis or septic shock. Furthermore, the combination of these three biomarkers achieved better predictive performance (AUC 0.890, P < 0.001) than conventional scoring systems. In summary, the combination of IL-6, NT-proBNP, and INR may serve as a potential predictor of 28-day mortality in critically ill patients with sepsis or septic shock.


2021 ◽  
Author(s):  
◽  
Divakaran Reddy

Tax compliance is the willingness of taxpayers to obey tax rules of a nation, whilst tax noncompliance is the unwilling behaviour of citizens to act under tax regulations. Taxpayer compliance enables the government to collect tax revenues, which is one of the most important sources of government income. Altering the non-compliant behaviour of citizens is an important barometer for increasing tax revenues that contribute to the socio-economic development of a nation. Numerous quondam studies have been conducted strikingly in the past few decades on taxpayer compliance. However, there is a dearth of sufficient research currently on tax noncompliance behaviour. Moreover, the phenomenon of tax noncompliance has limited exploration from the vantage point of meta-analysis of primary research studies conducted, focussing on interrogating, and systematically categorising their results. Resultantly, the purpose of this study was to examine the previously related primary studies to determine those factors that have been judged to have influenced the tax compliance behaviour of citizens. This study has adopted the quantitative research approach and followed the preferred reporting items for systematic review (PRISMA) method and meta-analysis to provide an accurate estimate of the relationship that exists in a population of relevant tax noncompliance behavioural studies. The population comprised of 45 international studies conducted between the period 2015 to 2020 is selected for analysis. The study results indicate that the quality of tax administration systems and public trust in institutional governance are factors that have influenced taxpayer compliance positively. Poor government accountability mechanisms entrenched tax gaps, and developing public trust in government institutions were found to be universal to promote voluntary taxpayer compliance. This study has contributed significantly to the open discussion on tax compliance among researchers, governments, and businesses.


2020 ◽  
Vol 19 (5) ◽  
pp. 1023-1029
Author(s):  
Yongbo Zhang ◽  
Zhuo Wu ◽  
Yihui Yang ◽  
Lu Ding

Purpose: To investigate the effect of trifluorobenzamidine (TBI) on a mouse model of ovalbumin (OVA)- induced allergic rhinitis. Methods: Allergic rhinitis was established in mice via sensitization on days 1, 5 and 14 through intraperitoneal injection of OVA (100 μg) in PBS. On day 15, the mice were subjected to intranasal exposure to OVA (1.5 mg dissolved in PBS). Prior to 10 days of intranasal exposure to OVA, the micewere treated with TBI at doses of 5, 10 and 20 μg/kg. Cytokine levels were determined using enzymelinked immunosorbent assay (ELISA) kits, while cyclooxygenase (COX)-2 and caspase-1 activity were assayed with western blotting. Results: Treatment with TBI significantly (p < 0.05) reduced OVA-mediated increases in nasal rub scores, and decreased serum levels of IgE, TNF-α, thymic stromal lymphopoietin (TSLP), IL-1β and histamine in mice. It also significantly regulated spleen weight and IL-4 secretion (p < 0.05) in OVAadministered mice. TBI significantly downregulated the expressions of IL-5, IL-13, TNFα, TSLP, IL-1β and IL-6 (p < 0.05). Administration of TBI caused a marked reduction in OVA-mediated increase in caspase-1 activity in mice intranasal tissues, and also significantly reduced OVA-induced excessive production of MIP-2 and ICAM-1 (p < 0.05). Moreover, TBI prevented OVA-induced infiltration of eosinophils and mast cells into intranasal tissues (p < 0.05). Conclusion: TBI reduces levels of IgE and various pro-inflammatory cytokines in OVA-administered mice. It also regulates Th1:Th2 ratio, inhibited activity of caspase-1, suppressed mast cell/eosinophil infiltration and reduced ICAM-1 and MIP-2 levels. Therefore, TBI possesses inhibitory potential against rhinitis allergy, and thus can potentially be developed as a new treatment strategy for asthma. Keywords: Trifluorobenzamidine, Anti-inflammation, Allergic rhinitis, Cytokines, Caspase-1, Itching


2020 ◽  
Vol 46 (Supplement_1) ◽  
pp. S141-S141
Author(s):  
Dana Allswede ◽  
Robert Yolken ◽  
Stephen Buka ◽  
Tyrone Cannon

Abstract Background Schizophrenia has been associated with pregnancy and birth complications, and fetal exposure to inflammation is thought to be a common underlying mechanism. However, it is unclear whether the risk associated with inflammation is specific to particular phases of pregnancy, as no prior studies have examined maternal serum samples across multiple assessments from the first trimester onward. This study examined differences in longitudinal patterns of maternal serum levels of TNFa, IL-1b, IL-5, IL-6, IL-8, IL-10, and IL-17a across pregnancy for offspring who were later ascertained as having a psychotic disorder diagnosis, non-psychotic siblings of these cases, and unrelated, non-psychotic individuals who served as controls. Methods Participants included 90 offspring, 79 siblings, and 273 matched controls from the Philadelphia cohort of the National Collaborative Perinatal Project. Psychotic disorder diagnoses in adulthood were assessed with review of medical records and were confirmed with a validation study. Cytokine levels were assessed using a multiplex bead assay in archived maternal serum samples collected across prenatal visits and birth. Results Levels of pro-inflammatory TNFa, IL-1b, and IL-6 were significantly higher in maternal serum of offspring who later developed psychosis relative to maternal serum of non-psychotic siblings and matched controls. These differences were maximal in first half of pregnancy (7–20 weeks), tapering to non-significant during the second half of pregnancy. Discussion These findings elucidate the importance of exposure to elevated maternal pro-inflammatory cytokine levels in early pregnancy to the etiology of psychosis.


2020 ◽  
Vol 11 ◽  
pp. 204201882092532 ◽  
Author(s):  
Aleksandra Żebrowska ◽  
Marcin Sikora ◽  
Anna Konarska ◽  
Anna Zwierzchowska ◽  
Tomasz Kamiński ◽  
...  

Aim: This study aimed to determine the effect of moderate intensity continuous exercise (Ex) and hypoxia (Hyp) on serum brain-derived neurotrophic factor (BDNF), insulin-like growth factor-1 (IGF-1) and its binding protein-3 (IGFBP-3), irisin and cytokines levels in patients with type 1 diabetes (T1D). Methods: A total of 14 individuals with T1D (age: 28.7 ± 7.3 years) and 14 healthy adults (age: 27.1 ± 3.9 years) performed 40-min continuous Ex at moderate intensity (50% lactate threshold) on a cycle ergometer in normoxia (Nor) and Hyp (FiO2 = 15.1%) Biochemical factors, glucose concentrations and physiological variables were measured at rest, immediately and up to 24 h after both Ex protocols. Results: Patients with T1D had significantly lower pre-Ex serum concentrations of BDNF ( p < 0.05, p < 0.01), and total IGF-1 ( p < 0.001, p < 0.05) and significantly higher irisin levels ( p < 0.05, p < 0.01) in Nor and Hyp, compared with healthy subjects. Ex significantly increased in T1D group serum BDNF (in Nor only p < 0.05) and total IGF-1 levels in Nor and Hyp ( p < 0.001 and p < 0.01, respectively). Immediately after Ex in Hyp, freeIGF-1 ( p < 0.05) and irisin levels ( p < 0.001) were significantly higher compared with the levels induced by Ex alone. Free IGF-1 and irisin serum levels remained elevated in 24 h post-Ex in Hyp. In T1D, significant blood glucose (BG) decrease was observed immediately after Ex in Hyp ( p < 0.001) and in 24 h recovery ( p < 0.001) compared with pre-Ex level. Conclusion: The study results suggest that moderate intensity continuous Ex has beneficial effect on BDNF and IGF-1 levels. Ex in hypoxic conditions may be more effective in increasing availability of IGF-1. The alterations in the post-Ex irisin levels and IGF-1 system may be contributing to more effective glycaemia control in patients with T1D.


2017 ◽  
Vol 41 (S1) ◽  
pp. S480-S480
Author(s):  
C. Blesl ◽  
A. Tmava ◽  
A. Baranyi ◽  
A. Meinitzer ◽  
A. Painold ◽  
...  

IntroductionPancreatic carcinoma (PC) belongs to the most aggressive tumours worldwide, with a five year survival of 7%. Mostly, diagnosis is made in late stages, as by now no early detection method is available. Symptoms of depression occur frequently before diagnosis of PC. PC and depression are both known to go along with changes in the kynurenine-pathway.ObjectivesThis study aimed to examine the kynurenine pathway (Figure 1) and evaluate a possible depression in newly diagnosed PC patients in comparison to healthy controls (HC).Methods26 PC patients and 26 age and sex matched HC participated in this study. We investigated serum-levels of kynurenine, kynurenic-acid, quinolinic-acid and tryptophan. To diagnose features of depression SKID-II and BDI were used.ResultsNone of the participants fulfilled criteria of a depressive episode. Regarding BDI-scores, 2 PC-patients showed features of mild depression. PC patients showed significantly lower tryptophan-levels (P = 0.05) and significantly increased quinolinic-acid levels (P = 0.01) compared to HC. Quinolinic-acid levels were correlated with BDI (r = 0.23, P = 0.02).ConclusionsOur study results imply IDO-activation and kynurenine-pathway activation by showing decreased tryptophan and high quinolonic-acid levels in our PC patients compared to HC. Larger studies are needed to gather further insight in the kynurenine pathway in PC.Disclosure of interestThe authors have not supplied their declaration of competing interest.Figure 1


2019 ◽  
Vol 73 (11) ◽  
pp. 1012-1019 ◽  
Author(s):  
Linda Dunder ◽  
Margareta H Lejonklou ◽  
P Monica Lind ◽  
Lars Lind

BackgroundMounting evidence from both experimental and epidemiological studies suggest that exposure to the endocrine disruptor bisphenol A (BPA) has a role in metabolic disorders. The aim of the present study was to assess whether urinary BPA concentrations were associated with dyslipidaemia in children (≤17 years old) and adults (≥18 years old) by performing a meta-analysis of data from six cycles (2003–2014) in the National Health and Nutrition Examination Survey (NHANES).MethodsWe conducted a meta-analysis of data from 4604 children and 10 989 adult participants who were part of a substudy of urinary BPA measurements from six NHANES cycles from 2003 to 2014. Linear regression models conducted in each cycle were used to perform a meta-analysis to investigate associations between urinary BPA and serum levels of low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC), triglycerides (TG) and apolipoprotein B (ApoB).ResultsThe meta-analysis did not disclose any significant associations between urinary BPA concentrations and LDL-C, HDL-C, TC, TG and ApoB in children. In adults, the meta-analysis revealed negative regression coefficients for all five lipid variables. However, no associations were significant following Bonferroni correction for multiple tests.ConclusionsIn the present meta-analysis of cross-sectional data from NHANES, no associations were found between urinary BPA and the five different lipid variables when investigated in both children and adults. However, considering the cross-sectional nature of the present study, results should be clarified in carefully designed longitudinal cohort studies with repeated BPA measurements.


2017 ◽  
Vol 2017 ◽  
pp. 1-14 ◽  
Author(s):  
Charles C. Emene ◽  
Irina E. Kravchenko ◽  
Gulnaz I. Aibatova ◽  
Albert A. Rizvanov

Increased free radical production had been documented in group A (β-hemolytic) streptococcus infection cases. Comparing 71 erysipelas patients to 55 age-matched healthy individuals, we sought for CAT, SOD1, and SOD2 single polymorphism mutation (SNPs) interactions with erysipelas’ predisposition and serum cytokine levels in the acute and recovery phases of erysipelas infection. Whereas female patients had a higher predisposition to erysipelas, male patients were prone to having a facial localization of the infection. The presence of SOD1 G7958, SOD2 T2734, and CAT C262 alleles was linked to erysipelas’ predisposition. T and C alleles of SOD2 T2734C individually were linked to patients with bullous and erythematous erysipelas, respectively. G and A alleles of SOD1 G7958A individually were associated with lower limbs and higher body part localizations of the infection, respectively. Serum levels of IL-1β, CCL11, IL-2Rα, CXCL9, TRAIL, PDGF-BB, and CCL4 were associated with symptoms accompanying the infection, while IL-6, IL-9, IL-10, IL-13, IL-15, IL-17, G-CSF, and VEGF were associated with predisposition and recurrence of erysipelas. While variations of IL-1β, IL-7, IL-8, IL-17, CCL5, and HGF were associated with the SOD2 T2734C SNP, variations of PDFG-BB and CCL2 were associated with the CAT C262T SNP.


2005 ◽  
Vol 23 (34) ◽  
pp. 8748-8756 ◽  
Author(s):  
Dominique Arpin ◽  
David Perol ◽  
Jean-Yves Blay ◽  
Lionel Falchero ◽  
Line Claude ◽  
...  

Purpose To investigate variations of circulating serum levels of interleukin-6 (IL-6), tumor necrosis factor alpha (TNFα), and interleukin-10 (IL-10) during three-dimensional conformal radiation therapy (3D-CRT) in patients with non–small-cell lung cancer and correlate these variations with the occurrence of radiation pneumonitis. Patients and Methods Ninety-six patients receiving 3D-CRT for stage I to III disease were evaluated prospectively. Circulating cytokine levels were determined before, every 2 weeks during, and at the end of treatment. Radiation pneumonitis was evaluated prospectively between 6 and 8 weeks after 3D-CRT. The predictive value of clinical, dosimetric, and biologic (cytokine levels) factors was evaluated both in univariate and multivariate analyses. Results Forty patients (44%) experienced score 1 or more radiation pneumonitis. No association was found between baseline cytokine levels and the risk of radiation pneumonitis. In the whole population, mean levels of TNFα, IL-6, and IL-10 remained stable during radiotherapy. IL-6 levels were significantly higher (P = .047) during 3D-CRT in patients with radiation pneumonitis. In the multivariate analysis, covariations of IL-6 and IL-10 levels during the first 2 weeks of 3D-CRT were evidenced as independently predictive of radiation pneumonitis in this series (P = .011). Conclusion Early variations of circulating IL-6 and IL-10 levels during 3D-CRT are significantly associated with the risk of radiation pneumonitis. Variations of circulating IL-6 and IL-10 levels during 3D-CRT may serve as independent predictive factors for this complication.


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