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Background & objectives: Diabetes mellitus (DM) is characterized by increase in blood glucose levels due to defective insulin secretion or insulin sensitivity. Interleukins (ILs) are known to play an important role in the pathogenesis of DM. The aim of this study was to investigate the serum concentration of IL-33 and its receptor soluble ST2 (sST2) in patients with diabetes and draw a correlation between their serum levels and different standard glycaemic indices of patients affected with type-2 diabetes with or without metabolic syndrome. Methods: Thirty type-2 diabetic individuals and 30 healthy controls were recruited for this study. Serum and plasma were separated by centrifugation of blood for quantitative measurement of IL-33, sST2 and other biochemical parameters. Results: It was observed that serum IL-33 levels were significantly less and sST2 levels were significantly high in type-2 diabetic individuals as compared to healthy controls. A significant correlation between the serum IL-33 concentration and fasting plasma glucose (FPG) and postprandial plasma glucose (PPG) levels were also found. Additionally, data also elucidated that serum levels of high-density lipoprotein, low-density lipoprotein or triglyceride in type-2 diabetics did not influence the serum levels of IL-33 and sST2, thereby excluding these factors as the major drivers of changes in serum IL-33 and sST2 concentration. Interpretation & conclusions: This study demonstrated alteration in serum levels of IL-33 and sST2 in type-2 diabetic individuals. Further mechanistic studies, focusing on the progression of type-2 diabetes could elucidate the involvement of IL-33 in the cellular acquisition of insulin resistance as observed in type-2 diabetics
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Aim To investigate the effects of IL-33/ST2 signal regulation by osteomortin on immune function and sodium channel in otitis media rats. Methods Fifty SD rats were randomly divided into NO group (normal rats with gavage of normal saline), MO group (model rats with gavage of normal saline), OS group (model rats with gavage of 40 mg • kg-
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Objective: The aim of the present study was to find a correlation of serum Suppression of tumorigenicity 2 (ST2) levels with severity of diastolic dysfunction on echocardiography and cardiac magnetic resonance imaging (CMRI) in heart failure with preserved ejection fraction (HFpEF) patients. Methods: Fifty patients aged _x0001_18 years fulfilling diagnostic criteria for HFpEF were included. ST2 levels, 2D echocardiography and CMRI were performed. Left ventricular ejection fraction, E/A, Septal E/E’, left atrial volume index (LAVI), tricuspid regurgitation (TR), assessment of diastolic dysfunction, T1 mapping in milliseconds and late gadolinium enhancement (LGE) in percentage were noted. The primary outcome measure was to study correlation of ST2 levels with severity of diastolic dysfunction, whereas the secondary outcome measures were to study correlation of ST2 levels with native T1 mapping and LGE on CMRI. Results: ST2 levels showed statistically significant and positive correlation with E/E’ (r ¼ 0.837), peak TR velocity (r ¼ 0.373), LAVI (r ¼ 0.74), E/A (r ¼ 0.420), and T1 values in milliseconds (r ¼ 0.619). There was no statistically significant correlation between ST2 level and LGE in % (r ¼ 0.145). The median ST2 levels in patients with E/E’ > 14 and E/E’ 14 were 110.8 and 36.1 respectively (p-value < 0.05). The mean ST2 levels were significantly higher in patients who had diastolic dysfunction grade III (126.4) and New York Heart Association class IV (133.3). Conclusions: Evaluation of ST2 adds important information to support the diagnosis of left ventricular diastolic dysfunction in patients with HFpEF
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ObjectiveTo investigate the therapeutic effect of Xiao Qinglongtang （XQLT） on ovalbumin （OVA）-induced allergic rhinitis （AR） in mice and its effect on the interleukin-33 （IL-33）/suppression of tumorigenicity 2 （ST2） signaling pathway. MethodSeventy-two female BALB/c mice of SPF grade were randomly divided into a control group， a model group， a positive control group （loratadine， 2.05 mg·kg-1）， and low-， medium-， and high-dose （5.005，10.01，20.02 g·kg-1） XQLT groups. All mice except for those in the control group were sensitized by intraperitoneal injection of OVA solution， and the AR model was induced by intranasal drops of OVA solution. Thirty minutes before local intranasal drops， drugs were administered once， and mice in the control group and the model group received phosphate buffered saline （PBS） at 20 mL·kg-1 for 7 days. After the last intranasal drop of OVA solution， the times of sneezing and nasal rubbing of mice within 10 min was recorded. After drug administration for 7 days， blood samples were collected， and nasal bones of mice were decalcified for the preparation of pathological sections. The content of OVA-specific immunoglobulin E （OVA-sIgE）， interleukin-4 （IL-4）， interleukin-5 （IL-5）， and interleukin-13 （IL-13） was detected by enzyme-linked immunosorbent assay （ELISA） kits. Hematoxylin-eosin （HE） staining， periodic acid-Schiff （PAS） staining， and Giemsa staining were used to observe the pathological changes， goblet cell hyperplasia， and eosinophil infiltration of nasal mucosa， respectively. Western blot was used to detect the expression levels of IL-33， ST2， and IL-1 receptor accessory protein （IL-1RAP） in nasal mucosa. ResultCompared with the control group， the model group showed increased times of sneezing and nasal rubbing （P<0.01）， edema and thickening of nasal mucosa， goblet cell hyperplasia and eosinophil infiltration， increased serum levels of OVA-sIgE， IL-4， IL-5 and IL-13 （P<0.01）， and increased protein expression of IL-33， ST2， and IL-1RAP in nasal mucosa （P<0.05，P<0.01）. After drug administration， compared with the model group， the high-dose XQLT group showed reduced times of sneezing and nasal rubbing （P<0.01）， improved pathological conditions of nasal mucosa， reduced serum levels of OVA-sIgE， IL-4， IL-5， and IL-13 （P<0.01）， and declining protein expression of IL-33， ST2， and IL-1RAP in nasal mucosa （P<0.05，P<0.01）. ConclusionXQLT has a therapeutic effect on OVA-sensitized AR mice， and the mechanism may be related to the regulation of the IL-33/ST2 signaling pathway and Th2 inflammatory cytokine to reduce Th2 inflammatory response and alleviate nasal mucosal injury.
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AIM: To investigate the relationship between serum soluble growth stimulation expressed gene 2 protein(sST2) level and coronary artery complex lesions and their severity. METHODS: A total of 430 patients, who were sequentially admitted to hospital for selective coronary artery angiography, were divided into control group (non-coronary heart disease group, 136 patients), simple lesions group of coronary heart disease (86 patients), complex lesions group (208 patients). To quantitative evaluate the complexity of coronary artery lesions, Syntax scores were further performed on patients in complex lesions groups, including 139 patients in the low-risk group, 36 patients in the medium-risk group, and 33 patients in the high-risk group. The serum soluble ST2 level of each group of patients was tested by means of ELISA. Spearman correlation analysis was used for the correlation between the level of soluble ST2 and the severity of coronary complex lesions. RESULTS: In 430 subjects, the soluble ST2 level of all patients with coronary heart disease (including simple lesions and complex lesions) was significantly higher than that of the control group [(3 449±1 250) vs. (2 743±961) pg/mL, P<0.001]; the sST2 levels of patients in the coronary artery simple lesions group, complex lesions low-risk group, medium-risk group and high-risk group were (3 200±1 406), (3 338±1 064), (3 728±1 228) and (4 261±1 235) pg/mL respectively, and the differences of sST2 levels among above four groups were statistically significant (P<0.001). Logistic regression analysis showed that sST2 was independently associated with coronary heart disease (OR=1.001, P<0.001) and sST2 was independently associated with the severity of coronary artery complex lesions (OR=1.001, P<0.001). Spearman-related analysis shows that the expression levels of sST2 are positively related to the severity of coronary artery lesions (rs: 0.543, P<0.001). The ROC curve showed that the area under the curve of sST2 for complex coronary lesions was AUC=0.726. CONCLUSION: Serum soluble ST2 level may be an important predictor of complicated coronary artery disease.
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Objective To investigate the effects of Sacubitril/Valsartan on amino terminal probrain natriuretic peptide (NT-proBNP),high sensitivity C-reactive protein (hs-CRP),soluble suppression of tumorigenicity 2(sST2)levels and on left ventricular(LV)structure in NYHA Ⅳ heart failure with reduced ejection fraction(HFrEF) patients.Methods A total of 67 HFrEF patients with NYHA Ⅳ were randomly divided into the control group (n =30)receiving conventional medical treatment,and the observation group(n=32)receiving Sacubitril/Valsartan instead of ACEI(or ARB if ACEI induced cough) in conventional medical treatment.NT-proBNP levels were determined by fluorescer-enhanced chemiluminescence.hs CRP levels were detected by latecx enhanced immunoturbidimetric assay.sST2 levels were determined by enzyme-linked immunosorbent assay (ELISA).The modified Simpson method was used to detect left ventricular end-diastolic diameter (LVEDD),LV posterior wall(LVPW)and LV ejection fraction(LVEF).Two groups of patients were treated and followed-up for 6 months.Results Clinical efficacy was better in the observation group than in the control group(effective rate,20 cases or 61.3％ vs.8 cases or 26.7％,P＜0.05).As compared with the control group,the observation group of patients had an increased LVEF[(46.7±9.2) ％ vs.(41.8±8.0)％,P＜0.05]and a decreased LVEDD[(52.6±6.7)mm vs.(58.8±7.5)mm,P＜0.05].After vs.before treatment,NT-proBNP,hs-CRP and sST2 levels were decreased in both control and observation groups [(1 427 ± 219) μg/L vs.(2 615 ± 273)μg/L,(1.14 ± 1.02) mg/L vs.(1.55±1.38)mg/L,(0.30±0.12)μg/L vs.(0.41±0.10)μg/L,all P＜0.05],and the decrements were much more in the observation group than in the control group (P＜0.05).The annual accumulated frequence and duration of hospitalization were less in the observation group than in the control group[(0.8±0.6)times vs.(1.8±1.0) times,(10.2±5.8)d vs.(16.5±7.2)d,P＜0.05].The maintenance dose of tolasemide was lower in the observation group than in the control group [(15.2±8.4)mg vs.(20.6±10.8)mg,P＜0.05].Conclusions Sacubitril/valsartan therapy is safe and effective and it can reduce hs-CRP and sST2 levels and improve the ventricular remodeling in HFrEF patients of HYHA Ⅳ.
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@#Interleukin-33(IL-33) is a new member of the interleukin-1 (IL-1) cytokine superfamily. It can activate mast cells, lymphocytes and macrophages to produce Th2 cytokines and plays a very important role in inflammation, infection, and autoimmune disease. The classical signal pathway of IL-33 includes the isotrimer of ST2 and interleukin-1 receptor accessory protein (IL-1 RAcP), which transduces signals into cells. The IL-33/ST2 signaling pathway affects bone metabolism by activating T and B lymphocytes. This article reviews the role of the IL-33/ST2 signaling pathway in bone metabolism. The results of a literature review showed that at present, scholars at home and abroad still dispute the role of IL-33 in bone metabolism. Some scholars believe that IL-33 can inhibit osteoclast formation, and IL-33 has been recently implicated in physiological bone remodeling. However, other scholars believe that IL-33 can promote osteoclast formation and differentiation, which leads to bone absorption. IL-33 and its signaling pathway are involved in bone metabolism of alveolar bone in periodontitis and periapical periodontitis. The specific mechanism remains unclear, and further studies are warranted.
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Interleukin-33 (IL-33), a novel identified member of IL-1 superfamily, is involved in the development and progress of various immune-related diseases, including inflammatory bowel disease (IBD), via its receptor ST2-mediated pathway, but the mechanism is not fully clarified. It has been reported that IL-33 plays a dual role in promoting inflammation and inducing protective effect in intestinal mucosa. This article reviewed the relationship between IL-33/ST2 signal pathway and IBD.
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Interleukin-33 (IL-33) is a multifunctional gene in the interleukin-1 family and is widely expressed in human tissues. Its receptor is ST2, is associated with asthma, diabetes, Alzheimer's disease, cardiovascular disease, inflammatory bowel disease, and cancer. IL-33, enhancing lipid metabolism and down-regulating adipogenic gene expression by inducing Th2 cytokine production, plays a protective role in fatty liver. In hepatitis, the IL-33/NKT/IFN-γ pathway exacerbates mouse hepatitis. While, the IL-33/ILC2/IL-13/STAT6 pathway reduces liver damage. The IL-33/ILC2/IL-13/IL-4Rα/STAT6 axis plays a facilitating role in cirrhosis. In liver cancer, IL-33/ILC2/IL-13 signaling pathway is found to promote cholangiocarcinoma in a favorable pathological environment, and hepatocellular carcinoma occurs by IL-33/IL-6/JAK/STAT/Mcl-1 signaling pathway.
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Obesity is a health problem of great concern to the whole society. Numerous studies have shown that obesity can lead to changes in the types and numbers of immune cell subsets and immune molecules in visceral adipose tissues, and IL-33/ST2 plays a crucial role in maintaining immune homeosta-sis. This paper reviewed the regulatory effects of IL-33/ST2 on adipocytes and immune cells in adipose tis-sues, as well as the changes of IL-33 in adipose tissues and the whole body during obesity in recent years.
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Interleukin-33 (IL-33) is a multifunctional gene in the interleukin-1 family and is widely expressed in human tissues.Its receptor is ST2,is associated with asthma,diabetes,Alzheimer's disease,cardiovascular disease,inflammatory bowel disease,and cancer.IL-33,enhancing lipid metabolism and down-regulating adipogenic gene expression by inducing Th2 cytokine production,plays a protective role in fatty liver.In hepatitis,the IL-33/NKT/IFN-γ pathway exacerbates mouse hepatitis.While,the IL-33/ILC2/IL-13/STAT6 pathway reduces liver damage.The IL-33/ILC2/IL-13/IL-4Rα/STAT6 axis plays a facilitating role in cirrhosis.In liver cancer,IL-33/ILC2/IL-13 signaling pathway is found to promote cholangiocarcinoma in a favorable pathological environment,and hepatocellular carcinoma occurs by IL-33/IL-6/JAK/STAT/Mcl-1 signaling pathway.
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Obesity is a health problem of great concern to the whole society. Numerous studies have shown that obesity can lead to changes in the types and numbers of immune cell subsets and immune molecules in visceral adipose tissues, and IL-33/ST2 plays a crucial role in maintaining immune homeostasis. This paper reviewed the regulatory effects of IL-33/ST2 on adipocytes and immune cells in adipose tissues, as well as the changes of IL-33 in adipose tissues and the whole body during obesity in recent years.
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Background Soluble suppression of tumorigenicity-2 (sST2) is a novel biomarker shown to be useful for prognostic assessment in heart failure (HF). However, very limited data exists about its prognostic utility in patients with HF in India. Methods We studied 150 patients [mean age 67.7 ± 13.3, 93 (62%) males], hospitalized with clinical HF, irrespective of their left ventricular ejection fraction (LVEF). HF was confirmed by N-terminal probrain natriuretic peptide (NT-proBNP) value above 125 ng/L. Primary end point was death or cardiac transplant at 1-year follow-up, with additional telephonic follow-up performed at 2 years. The clinical outcomes were correlated with the sST2 values obtained at the time of initial hospitalization. Results HF was ischemic in origin in 82.0% patients. The primary outcome occurred in 9.3% patients at the end of 1-year follow-up and in 16.7% patients at the end of 2 years. The patients who had events had significantly higher NT-proBNP and sST2 values, but there was no difference in the clinical characteristics, cause of HF, baseline LVEF, or serum creatinine. The patients with elevated sST2 levels (>35 ng/mL) had substantially higher event rates than those with normal sST2 levels (13.7% vs 0.0% at 1-year, P = 0.005; 22.5% vs 4.2% at 2-years, P = 0.004). On multivariate analysis, sST2 was the strongest predictor of adverse outcomes at both 1-year and 2-year follow-ups. Conclusion In patients hospitalized for HF, elevated sST2 >35 ng/mL at the time of initial hospitalization was associated with significantly high mortality over a 2-year period. The prognostic value of sST2 was incremental to that of NT-proBNP. These findings suggest that a single elevated sST2 value at the time of hospitalization should alert the physicians about the high risk of adverse outcomes and should help facilitate timely intensification of HF treatment.
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Objective To study the predictive value of serum soluble ST2 (sST2) in patients with sepsis.Methods A total of 63 patientswith sepsis and 30 healthy subjects as a control group in the emergency Department,Beijing Hospital,National Center of Gerontology,were enrolled in the study.Serum sST2 concentrations were measured by ELISA method.Patients were divided into sepsis group (n=44) and septic shock group (n=19).According to 28-day mortality after the diagnosis of sepsis,patients were divided into death group (n=18) and survival group (n=45).Respiratory rate,oxygenation index,white blood cell count,procalcitonin (PCT),C reactive protein (CRP),serum creatinine (CRE),total bilirubin (TBIL) of patients and control subjects were measured.SPSS 23.0 software was used for the statistical analyses.The measurement data was analyzed by t test and the enumeration data was analyzed by Chi square test.The survival status was analyzed by Logistic binary regression analysis and ROC curve analysis.Results The serum sST2 level (1 382.12±384.07) pg/mL in sepsis group was significantly higher than that in control group (569.28±163.46) pg/mL (P＜0.05).in septic shock group,28-day mortality rate (63.16％) and serum sST2 level (1 675.49±457.59) pg/mL was higher than those in sepsis group (13.64％) (1255.44 ± 265.70) pg/ml (P＜0.05).The PCT (16.37±16.36) ng/mL and serum sST2 level (1794.47±335.18)pg/mL in death group were higher than those in survival group (P＜0.05).The ROC curve showed that the AUC of sST2 was larger than that of PCT (0.917 vs.0.884),the sensitivity was higher than that of PCT (88.9％ vs.72.2％),and the specificity was lower than that of PCT (82.2％ vs.93.3％).The combination AUC of sST2 and PCT was 0.944.Conclusions Serum sST2 has a certain value in the diagnosis of sepsis,and can be used to predict the prognosis of patients with sepsis.The higher the sST2 value,the worse the prognosis.Compared with PCT,sST2 is more sensitive in the prognosis of sepsis,but the specificity is not high enouph.The measurement of sST2 level coupled with PCT level may be more useful.
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<p><b>Background</b>Serum soluble ST2 (sST2) levels are elevated early after acute myocardial infarction and are related to adverse left ventricular (LV) remodeling and cardiovascular outcomes in ST-segment elevation myocardial infarction (STEMI). Beta-blockers (BB) have been shown to improve LV remodeling and survival. However, the relationship between sST2, final therapeutic BB dose, and cardiovascular outcomes in STEMI patients remains unknown.</p><p><b>Methods</b>A total of 186 STEMI patients were enrolled at the Wuhan Asia Heart Hospital between January 2015 and June 2015. All patients received standard treatment and were followed up for 1 year. Serum sST2 was measured at baseline. Patients were divided into four groups according to their baseline sST2 values (high >56 ng/ml vs. low ≤56 ng/ml) and final therapeutic BB dose (high ≥47.5 mg/d vs. low <47.5 mg/d). Cox regression analyses were performed to determine whether sST2 and BB were independent risk factors for cardiovascular events in STEMI.</p><p><b>Results</b>Baseline sST2 levels were positively correlated with heart rate (r = 0.327, P = 0.002), Killip class (r = 0.408, P = 0.000), lg N-terminal prohormone B-type natriuretic peptide (r = 0.467, P = 0.000), lg troponin I (r = 0.331, P = 0.000), and lg C-reactive protein (r = 0.307, P = 0.000) and negatively correlated to systolic blood pressure (r = -0.243, P = 0.009) and LV ejection fraction (r = -0.402, P = 0.000). Patients with higher baseline sST2 concentrations who were not titrated to high-dose BB therapy (P < 0.0001) had worse outcomes. Baseline high sST2 (hazard ratio [HR]: 2.653; 95% confidence interval [CI]: 1.201-8.929; P = 0.041) and final low BB dosage (HR: 1.904; 95% CI, 1.084-3.053; P = 0.035) were independent predictors of cardiovascular events in STEMI.</p><p><b>Conclusions</b>High baseline sST2 levels and final low BB dosage predicted cardiovascular events in STEMI. Hence, sST2 may be a useful biomarker in cardiac pathophysiology.</p>
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Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Antagonistas Adrenérgicos beta , Usos Terapéuticos , Biomarcadores , Sangre , Proteína 1 Similar al Receptor de Interleucina-1 , Sangre , Pronóstico , Estudios Prospectivos , Infarto del Miocardio con Elevación del ST , Sangre , Quimioterapia , PatologíaRESUMEN
BACKGROUND AND OBJECTIVES: We aimed to investigate the relationship between the recurrence of atrial fibrillation (AF) and fibrosis marker soluble ST2 (sST2) in patients with nonvalvular paroxysmal AF (PAF). METHODS: We prospectively included 100 consecutive patients with PAF diagnosis and scheduled for cryoballoon catheter ablation for AF (47 males, 53 females; mean age 55.1±10.8 years). sST2 plasma levels were determined using the ASPECT-PLUS assay on ASPECT Reader device (Critical Diagnostics). The measurement range of these measurements was 12.5–250 ng/mL. Patients had regular follow-up visits with 12-lead electrocardiogram (ECG), medical history, and clinical evaluation. Twenty-four hours Holter ECG monitoring had been recorded 12 months after ablation. RESULTS: AF recurrence was detected in 22 patients after 1 year. Age, smoking history, diabetes mellitus,hypertension frequency, angiotensin converting enzyme inhibitor-angiotensin receptor blocker use, CHA2DS2VASc and HAS-BLED scores, serum sST2 level, left atrium (LA) end-diastolic diameter, LA volume and LA volume index were related to AF recurrence. In multivariable logistic regression analysis, sST2 was found to be only independent parameter for predicting AF recurrence (odds ratio, 1.085; p=0.001). Every 10-unit increase in sST2 was found to be associated with 2.103-fold increase in the risk of AF recurrence. The cut-off value of sST2 obtained by receiver operating characteristic curve analysis was 30.6 ng/mL for prediction of AF recurrence (sensitivity: 77.3%, specificity: 79.5%). The area under the curve was 0.831 (p < 0.001). CONCLUSIONS: sST2, which is associated with atrial fibrosis, can be thought to be a useful marker for detection of patients with high-grade fibrosis who will get less benefit from cryoablation.
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Femenino , Humanos , Masculino , Fibrilación Atrial , Ablación por Catéter , Catéteres , Criocirugía , Diagnóstico , Electrocardiografía , Fibrosis , Estudios de Seguimiento , Atrios Cardíacos , Modelos Logísticos , Peptidil-Dipeptidasa A , Plasma , Estudios Prospectivos , Recurrencia , Curva ROC , Sensibilidad y Especificidad , Humo , FumarRESUMEN
Interleukin 33 (IL 33) is a recently described member of the IL 1 family and widely exists in cells and tissues.IL 33/ST2 axis is mainly associated with the secretion of IL 4,IL 5 and IL 13,which are involved in the initiation or progression of specific Th2 responses.It contributes to the macrophage alternative polarization,dendritic cell regulation,and direct effects on T cells.These effects explain how IL 33/ST2 axis plays contrasting roles in lung diseases.Although IL 33/ST2 axis has been extensively studied in various lung inflammatory diseases,a comprehensive overview on the role of this cytokine in infectious pneumonia is actually lacking.Therefore,we summarize the recent advances on the role of IL 33/ST2 axis in pneumonia caused by various viral,bacterial,fungal and helminth.
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IL-33,a recently discovered member of the IL-1 family,is a multifunctional cytokine.It is a-ble to activate variety of cells,including Th2 cells,eosnophils,basophils and mast cells,and then promoting the inflammatory response.Through its receptor ST2,IL-33 activates NF-κB and MAPK signaling pathway,induces production of Th2 cytokines and plays an important role in the occurrence as well as the development of many diseases such as asthma.As such,it is hoped that IL-33 will be a novel therapeutic target for brochial asthma. However,the role of IL-33 in asthma pathogenesis remains unclear yet.Thus,the present review focuses on the molecular structure,expression,biological activity and contribution of IL-33 to the pathogenesis of asthma.
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Heart failure is a serious and terminal stage of various cardiovascular diseases,is one of the most important heart diseases,and it also the most common reason for hospitalization.In recent years,studies on new markers in the diagnosis,treatment and prognosis of heart failure have made great progress,such as B-type brain natriuretic peptide can partially reflect hemodynamic imbalance,troponin can indicate cardiomyocyte injury,soluble ST2 and galectin-3 indicate myocardium remodeling and fibrosis,C-reactive protein,cystatin C and procalcitonin,and copeptin have significant prognostic value for outcomes,microRNA in the regulation of gene expression influence heart failure.