Serum Interleukin-33 Concentration Research Articles

Exploring TSLP and IL-33 Serum Levels and Genetic Variants: Unveiling Their Limited Potential as Biomarkers for Mild Asthma in Children.

As the burden of mild asthma is not well understood, the significance of expanding research in the group of patients with mild asthma is emphasized. Thymic stromal lymphopoietin (TSLP) and interleukin 33 (IL-33) are involved in the pathogenesis of atopy and the immune response to inhaled environmental insults, such as allergens, in asthmatic patients. Objectives: The objective of this study was to explore the correlation between specific polymorphisms within the genes encoding TSLP and IL-33, as well as the concentrations of TSLP and IL-33 in the serum, and the occurrence of pediatric mild asthma. Methods: The analysis encompassed 52 pediatric patients diagnosed with mild bronchial asthma, including both atopic and non-atopic cases, and a control group of 26 non-asthmatic children. Recruitment was conducted through a comprehensive questionnaire. Parameters such as allergic sensitization, serum levels of circulating TSLP and IL-33, and the identification of single-nucleotide polymorphisms in TSLP (rs11466750 and rs2289277) and IL-33 (rs992969 and rs1888909) were assessed for all participants. Results: Significantly lower mean serum TSLP concentrations were observed in asthmatic subjects compared to the control group, with atopic asthma patients showing even lower TSLP levels than non-atopic counterparts. No significant differences were found in mean serum IL-33 concentrations between the two groups. Considering the allele model, for both tested SNPs of IL-33, we observed that patients with asthma, atopic asthma, and atopy statistically less frequently possess the risk allele. Conclusions: Our study findings suggest that IL-33 and TSLP do not serve as ideal biomarkers for mild asthma in children. Their effectiveness as biomarkers might be more relevant for assessing disease severity rather than identifying asthma in pediatric patients. Further research focusing on the association between TSLP and IL-33 gene polymorphisms and asthma is expected to significantly advance disease management.

The correlation between maternal serum sST2, IL‐33 and NT‐proBNP concentrations and occurrence of pre‐eclampsia in twin pregnancies: A longitudinal study

The primary objective of this study was to determine the longitudinal profile of serum sST2 (soluble suppression of tumorigenicity 2), IL-33 (interleukin-33) and NT-proBNP (N-terminal pro-brain natriuretic peptide) concentrations in twin pregnancies with pre-eclampsia (PE) and those normotensive twins. The secondary objective was to test whether the change of serum sST2,IL-33 and NT-proBNP is related to PE in twin pregnancies. This is a longitudinal nested case-control study and all 156 dichorionic (DC) pregnancies were from a prospective cohort of twin pregnancies who received antenatal care and gave two live births at Peking University Third Hospital between October 2017 and September 2020. Four to five milliliters of peripheral blood of each pregnant woman were collected during the following three intervals: (1) 6-11+6 weeks; (2) 24-27+6 weeks; (3) 28-31+6 weeks. We found that sST2 and NT-proBNP levels increased as pregnancy progressed in normotensive twin pregnancies and further increased in PE group, while no differences were found in IL-33 levels throughout pregnancy. Then the correlation of biomarker levels with the occurrence of PE was assessed. Our results indicated that combining maternal serum sST2 and NT-proBNP levels yielded the highest predictive value on the occurrence of PE significantly higher than the predictive value of any markers alone. Interestingly, the predictive value of second trimester (AUC=0.876, 95%CI 0.824-0.928, LR-0.338, LR+7.67, p<0.001)was higher than that of early-third trimester (AUC=0.832, 95%CI 0.769-0.896, LR-0.29, LR+3.845, p<0.001). Serum sST2 and NT-proBNP concentrations during second and early-third trimester were associated with the occurrence of PE in twin pregnancies.

Serum Interleukin-33 is a Predictor of Depression in Patients with Acute Ischemic Stroke.

The study aimed to investigate the relationship between serum interleukin-33 (IL-33) concentrations and poststroke depression (PSD) in patients with acute ischemic stroke (AIS). Serum IL-33 concentrations were determined using an enzyme-linked immunosorbent assay. Patients were assigned to the PSD group after a six-month follow-up if their score on the 17- item Hamilton Rating Scale for Depression was ≥7 or to the non-PSD group if their score was <7. IL-33 was used to predict the risk of PSD using multivariate logistic regression analysis, while a receiver operating characteristic (ROC) curve was used to analyze the accuracy of PSD prediction. In addition, the modified Rankin scale (mRS) was used for follow-up scoring six months after disease onset. A total of 151 AIS patients and 40 healthy controls were included in this study. ROC curve results showed that the area under the curve was 0.684 (95% confidence interval: 0.594-0.774,Ρ=0.001) for IL-33 as a predictor of PSD. When the IL-33 concentration was ≤71.85 ng/L, prediction sensitivity and specificity were 77.5% and 57.3%, respectively. Multivariate logistic regression analysis showed that IL-33 concentration of ≤71.85 ng/L was an independent predictor of PSD (95% CI: 1.129-7.515, P=0.027). The follow-up mRS data showed that serum IL-33 is a protective prognosis factor in patients with AIS (95% CI: 0.954-0.997, P=0.024). Serum IL-33 is an independent predictor of PSD and a protective prognosis factor in patients with AIS.

Serum Interleukin-33 is a Novel Predictive Biomarker of Hemorrhage Transformation and Outcome in Acute Ischemic Stroke

IntroductionHemorrhage Transformation (HT) in acute ischemic stroke (AIS) depends on multiple factors. Some studies have shown that serum interleukin-33 (IL-33) is of central significance as a neuroprotective factor. However, the relationship between serum IL-33 and HT in AIS has not been evaluated. ObjectiveTo investigate the relationship between serum IL-33 concentration and HT in AIS. MethodsWe recruited 151 consecutive non-thrombolytic patients with AIS clinically diagnosed in The First Affiliated Hospital of Chongqing Medical University from December 2018 to October 2019. If the patients showed radiographic presentation of HT within two weeks following admission, they were assigned to the HT group; others were assigned to the non-HT group. There were 40 healthy control subjects recruited during the same period. Serum IL-33 concentration was detected by ELISA and the independent risk value of HT in AIS was predicted by multivariate logistic regression. The accuracy was analyzed by receiver operating characteristic (ROC) curves. In three months after admission, the functional outcome was measured by modified Rankin scale (mRS). ResultsROC curve showed that the area under the curve (AUC) of serum IL-33 was 0.739 (95% CI: 0.657–0.821, P < .001) in predicting HT in AIS. When serum IL-33 concentration was ≤ 67.66 ng/L, the sensitivity and specificity of the prediction were 81.3% and 63%, respectively. Multivariate logistic regression analysis showed that serum IL-33 concentration ≤ 67.66 ng/L was an independent predictor of HT in AIS (OR = 5.773, 95% CI: 1.685–19.792, P = .005). The follow-up results of mRS showed a higher probability of an unfavorable outcome in those with HT compared to those without HT (OR = 6.520, 95% CI: 2.530-16.803, P < .001). ConclusionsHT in AIS is negatively correlated with outcome. Furthermore, serum IL-33 is an independent predictive biomarker of HT and outcome in AIS.

Serum Concentrations of Interleukin-33 and its Soluble Receptor sST2 in Patients with Persistent Atrial Fibrillation

Objectives: Interleukin-33 (IL-33) is a new member of the IL-1 cytokine family, which is thought to be involved in the pathogenesis of various inflammatory diseases, through its soluble receptor ST2. There is increasing evidence that inflammation is a relevant player in structural atrial remodeling that represents the main mechanism for atrial fibrillation (AF) persistence. This study was designed to investigate the state of IL-33/ST2 axis serum concentrations in patients with persistent AF. Design and Methods: We investigated the concentrations of IL-33, its soluble ST2 receptors, and high-sensitivity C-reactive protein levels (hsCRP) in the sera of 92 patients with persistent atrial fibrillation, and 68 controls. Results: Serum concentrations of IL-33, sST2, and hsCRP were all significantly elevated in patients with persistent AF compared to controls (P <0.0001 for all). Moreover, serum IL-33 concentrations was positively correlated with the inflammatory marker hsCRP (r=0.606, P =0.002). Conclusion: These preliminary results may support the role of inflammation in AF pathogenesis and IL-33/sST2 axis may be involved in the inflammatory process in AF.

Association of polymorphism of genes of folate cycle and blood serum content of interleukin-33 in patients with high summary cardiovascular risk on the combined therapy of arterial hypertension

Aim. The study of genetic factors of cardiovascular diseases is of great importance, as the screening of major risk factors that cause the development of cardiovascular accidents across the globe does not enable identifying at least half of those who appear to suffer from the diseases in the future. In order to solve this particular problem, an effect of combined therapy of hypertension on the interleukin 33 (IL-33) in patients who appear to be at high risk of developing cardiovascular diseases as well as the presence of polymorphisms of genes of the folate cycle (MTHFR C677T, A1298G, MTR А2756G, MTRR A66G) have been studied.Methods and results. 41 women suffering from arterial hypertension as well as 10 patients at risk of SCORE<5% were examined. Using the enzyme immunoassay, serum IL-33 concentration before and after 6 months of treatment by combined medication (Noliprel A Forte, Servier) was studied. In addition, all the patients underwent the molecular genetic analysis of blood samples. As the result, the patients with arterial hypertension and ones being at high total cardiovascular disease risk showed the increased concentration of IL-33 in blood. Moreover, the relationship between its concentration in blood and polymorphism of gene MTRR A66G was established.Conclusion. This proves the key role of the polymorphism of gene MTRR A66G in influencing the IL-33 concentration index in blood.

Profibrotic interleukin-33 is correlated with uterine leiomyoma tumour burden

Are interleukin-33 (IL-33) serum levels higher in women with uterine leiomyoma compared with controls without leiomyoma? Serum IL-33 is elevated in women with uterine leiomyoma and correlated with features of uterine leiomyoma tumour burden, namely fibroid number, size and weight. Uterine leiomyomas are the most common benign tumours in premenopausal women associated with major tissue fibrosis. IL-33 is a cytokine involved in fibrotic disorders. The potential role of IL-33 in leiomyoma has not been reported before. This is a prospective laboratory study conducted in a tertiary-care university hospital between January 2005 and December 2010. We investigated non-pregnant, 42-year-old patients (n = 151) during surgery for a benign gynaecological condition. After complete surgical exploration of the abdominopelvic cavity, 59 women with histologically proved uterine leiomyoma and 92 leiomyoma-free control women were enrolled. Women with endometriosis or past history of ovarian malignancy and borderline tumours were not included. The control group included women with benign ovarian cysts, paratubal cysts or tubal defects without any evidence of uterine leiomyoma. For each patient, a structured questionnaire was completed during a face-to-face interview conducted by the surgeon during the month preceding surgery. Serum samples were obtained in the month preceding the surgical procedures according to the menstrual phase or hormonal therapy. IL-33 was measured in sera by enzyme-linked immunosorbent assay, and correlation of IL-33 concentration with the extent and severity of the disease was investigated. IL-33 was detected in 32 (54.2%) women with leiomyoma and 18 (19.6%) controls (P < 0.001). Serum IL-33 was higher in women with leiomyoma (median, 140.1 pg/ml; range, 7.5-2247.7) than in controls (median, 27.8 pg/ml; range, 7.5-71.6; P = 0.002). We found positive correlations between serum IL-33 concentration and leiomyoma features, such as fibroid weight (r = 0.630; P = 0.001) and size (r = 0.511; P = 0.018) and the number of fibroids (r = 0.503; P = 0.003). There was a possible selection bias due to inclusion of only surgical patients. Therefore our control group consisted of women who underwent surgery for benign gynaecological conditions. This may lead to biases stemming from the fact that certain of these conditions, such as tubal infertility or ovarian cysts, might be associated with altered serum IL-33 levels. We demonstrate for the first time that elevated serum IL-33 levels are associated with the existence of uterine leiomyoma. However, even if an association does not constitute proof of cause and effect, investigating the mechanisms that underlie fibrogenesis associated with leiomyomas is a step towards understanding this enigmatic disease. This study opens the doors to future, more mechanistics studies to establish the exact role of IL-33 in uterine leiomyomas pathogenesis. No funding, no conflict of interest.

Increased serum interleukin-33 levels in patients with Graves’ disease

Interleukin-33 (IL-33), a 30 kDa cytokine, is a member of IL-1 family. It is considered to be an autoimmune biomarker associated with T helper 2 (Th 2) response. γ-interferon is also produced by T helper 1 (Th 1) cells to induce cellular responses. γ-interferon is a 143-amino acid residue glycoprotein with several biological functions including potent anti-viral activity, stimulation of macrophage activity, modulation of Major Histocompatibilty Complex class I/class II expression, and regulation of a diversity of specific immune responses. The aim of this study was to investigate the serum levels of IL-33 and γ-interferon in different thyroid disorders. Twenty patients with Graves' disease, 21 patients with Hashimoto hypothyroidism, 21 euthyroid Hashimoto patients, and 27 control subjects were recruited to this study. Blood samples were drawn and IL-33 and γ-interferon tests were analyzed from 89 participants. Serum IL-33 and γ-interferon analyses were performed by enzyme-linked immunosorbent assay. There was no statistically significant difference between groups for serum γ-interferon levels. Serum IL-33 concentrations were significantly higher in Graves' disease group compared to the other groups (p<0.000) There was a positive correlation between serum IL-33 and free triiodothyronine (fT3) and thyroxine (fT4). Also, negative correlation between serum IL-33 and thyroid-stimulating hormone (TSH) was statistically significant (p<0.000). The correlation of serum IL-33 with thyroid hormone levels may be a useful indicator for Graves' disease. These findings may help to make evident the pathophysiologic processes of the autoimmune thyroid diseases and improve therapeutic methods. .

Changes in serum Interleukin-33 concentration before and after treatment with pegylated interferon alfa-2a plus ribavirin in patients with chronic hepatitis C genotype 1b infection

BackgroundIL-33 is a novel member of the IL-1 family, which has been shown to play an important role in T helper 2 (Th2)-associated immune responses. Recent studies have suggested a possible role for IL-33 in the pathogenesis of liver damage during acute and chronic hepatitis; furthermore, IL-33 may be involved in the development and progression of liver fibrosis.ObjectivesTo evaluate serum IL-33 levels in a group of patients with chronic hepatitis C (CHC) genotype 1b at enrolment and after a course of pegylated (PEG)-IFN plus ribavirin.Patients and Methods60 patients with chronic hepatitis C (CHC) and 65 healthy controls were examined and compared for serum IL-33 levels by ELISA. All CHC patients were submitted to liver biopsy either before starting antiviral treatment or during post-treatment follow up. We evaluated whether post-treatment IL-33 concentration was associated with histologic outcome as well as with virologic response to therapy.ResultsSerum IL-33 levels were significantly higher among CHC patients in comparison with healthy controls. IL-33 concentration was lower among patients with a METAVIR fibrosis score F1-F2, compared with those having a more advanced liver disease (METAVIR stage F3-F4). In addition, sustained virologic response (SVR) was associated with a significant drop in IL-33 levels, whereas no changes were found among relapsers and nonresponders. Analogously, patients experiencing liver histologic improvement after antiviral therapy had lower post-treatment IL-33 levels in comparison with baseline values. Contrarily, no variations were detected among subjects with worsened or stable histologic features.ConclusionsIL-33 may represent a new and easy-to-detect biomarker for the diagnosis of liver damage in CHC patients, as it appears to be modulated in parallel with biochemical and histologic parameters, such as ALT levels and liver fibrosis. Furthermore, considering that serum IL-33 concentration was significantly reduced following a successful course of antiviral treatment, this cytokine may also represent a sensitive indicator of SVR.

Serum and peritoneal interleukin-33 levels are elevated in deeply infiltrating endometriosis

Interleukin 33 (IL-33) is a cytokine involved in fibrotic disorders. We have analyzed IL-33 levels in the sera and peritoneal fluids of women with various forms of endometriosis and investigated the correlation with disease activity. We conducted a prospective laboratory study in a tertiary-care university hospital between January 2005 and December 2010. Five hundred and ten women with histologically proven endometriosis and 132 endometriosis-free controls were enrolled in this study. Complete surgical exploration of the abdominopelvic cavity was performed in each patient. Blood samples and peritoneal fluids were obtained before and during surgical procedures, respectively. IL-33 was measured by an enzyme-linked immunosorbent assay in sera and peritoneal fluids, and the concentrations correlated with the extent and the severity of endometriotic lesions. IL-33 was detectable in 23.1% of serum samples from all 642 women studied and 75.0% of peritoneal fluid samples studied (44 women with endometriosis and 36 controls). Serum IL-33 was higher in deeply infiltrating endometriosis (DIE) (median, 104.9 pg/ml; range, 8.0-104.9) than in endometriosis-free women (median, 61.3 pg/ml; range, 7.5-526.0; P = 0.022) or in women affected by superficial endometriosis (median, 36.8 pg/ml; range, 7.5-179.0; P < 0.001). Peritoneal IL-33 was higher in DIE than in endometriosis-free women (median, 642.0 pg/ml; range, 25.9-3350.6 versus median, 194.2 pg/ml; range, 12.7-1818.2, respectively; P = 0.003). We found positive correlations between serum IL-33 concentration and intensity of dysmenorrhea (r = 0.174; P = 0.028) and gastrointestinal symptoms (r = 0.199; P = 0.027), total number of DIE lesions (r = 0.224; P = 0.016) and the worst DIE lesion (r = 0.299; P < 0.001). In spite of the number of samples with undetectable levels, serum IL-33 is abnormally elevated in women with endometriosis and principally in DIE. Elevated serum IL-33 is correlated with the intensity of preoperative painful symptoms, and with the extent and severity of the DIE. IL-33 may be considered as a novel cytokine involved in the pathogenesis of DIE.