Dataset Information

Different expression levels of interleukin-35 in asthma phenotypes.

ABSTRACT:

Background

Interleukin (IL)-35 is a newly discovered inhibitory cytokine which is produced by regulatory B and T lymphocytes and belongs to the IL-12 family. It plays a suppressive role in human inflammatory diseases; however, its role in asthma phenotypes is unclear. Our study focuses on the sputum IL-35 level in patients and investigates different airway inflammation capacities of sputum IL-35 in patients with different asthma phenotypes.

Objective

We aimed to determine the sputum IL-35 levels in asthmatic patients with clinical remission phenotypes and control subjects and to investigate possible correlations among lung function, age, sex, fractional exhaled nitric oxide (FeNO), and smoking history in these phenotypes.

Methods

Sputum samples were collected from patients with clinical asthma remission (n = 89, 37 males, age 52.24 ± 13.32 years) and a healthy control group (n = 19, 9 males, age 44.58 ± 16.3 years). All subjects underwent sputum induction. Induced sputum was assessed for inflammatory cell count, and sputum levels of IL-35 and other cytokines were measured by ELISA and Cytometric Bead Array, respectively.

Results

Sputum IL-35 (median (q1, q3)) levels showed no significant difference between asthma patients (4.89 ng/mL (2.97, 22.75)) and healthy controls (6.01 ng/mL (4.09, 30.47)). However, the sputum IL-35 level was significantly reduced in patients with eosinophilic asthma (EA) (3.95 ng/mL (2.80, 11.00)) compared to patients with neutrophilic asthma (NA) (40.59 ng/mL (20.59, 65.06), p = 0.002), paucigranulocytic asthma (PA) (6.25 ng/mL (3.10, 24.60), p = 0.012), and mixed granulocytic asthma (MA) (22.54 ng/mL (2.58, 52.45), p = 0.026). IL-35 levels in sputum showed a positive correlation with sputum neutrophil cells and a negative correlation with FeNO, FEV1% predicted, and FVC predicted. Furthermore, sputum IL-35 had a significant positive association with Th1-related factors and a negative correlation with Th2-related factors.

Conclusions

Sputum IL-35 is likely involved in different pathophysiological mechanisms of NA and EA and exerts different effects in asthma phenotypes.

SUBMITTER: Li W

PROVIDER: S-EPMC7160921 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:The activation of monocytes and macrophages is associated with steroid-resistant (SR) asthma. Interleukin-35 (IL-35) is an important anti-inflammatory cytokine, but its regulatory effects on monocytes in patients with SR asthma is not fully understood. Based on clinical response to oral prednisolone, 34 patients with steroid-sensitive (SS) asthma and 20 patients with SR asthma were enrolled in the present study. Serum IL-35 levels were analyzed using the Luminex 200 platform. Monocytes from patients with asthma were pretreated with IL-35 followed by dexamethasone (DEX) and lipopolysaccharide (LPS), then corticosteroid sensitivity was evaluated according to the half-maximal inhibitory concentration of DEX with respect to LPS-induced IL-6 maximal production in monocytes (DEX-IC50). The percentage of maximal inhibition of IL-6 by DEX was presented as Emax. Phosphorylated-P38 mitogen activated kinase (p-p38 MAPK) and mitogen-activated protein kinase phosphatase-1 (MKP-1) were examined by flow cytometry and reverse transcription-quantitative PCR analysis, respectively. Glucocorticoid receptor (GR) binding to the glucocorticoid response element (GRE) was assessed by chromatin immunoprecipitation. Compared with patients with SS asthma, patients with SR asthma had lower IL-35 expression levels (P<0.05). Correlation analysis results demonstrated that the expression levels of IL-35 showed a weak negative correlation with log DEX-IC50 (r=-0.351; P<0.01) and a moderate positive correlation with Emax value (r=0.4501; P<0.01) in all patients with asthma. Moreover, IL-35 enhanced DEX-suppressed IL-6 production and the DEX-induced upregulation of the MKP-1 mRNA expression level in monocytes from both patient groups (P<0.01). In addition, IL-35 inhibited p-p38 MAPK expression in monocytes, and these effects were mediated via an increase in DEX-induced GR binding to GRE. Therefore, IL-35 may be involved in the corticosteroid enhancing effects in monocytes of patients with SR and SS asthma, suggesting potential benefits of IL-35 supplementation in asthmatics with DEX.

Project description:Abstract Background Previous studies reported that patients with asthma showed higher levels of interleukin (IL)‐33 in peripheral blood, compared to healthy control (HCs). However, we also noticed that there were no significant differences of IL‐33 levels between controls and asthma patients in a recent study. We aim to conduct this meta‐analysis and evaluate the feasibility of IL‐33 in peripheral blood that may act as a promising biomarker in asthma. Methods Articles published before December 2022 were searched in these databases (PubMed, Web of Science, EMBASE, and Google Scholar). We used STATA 12.0 software to compute the results. Results The study showed that asthmatics showed higher IL‐33 level in serum and plasma, compared to HCs (serum: standard mean difference [SMD] 2.06, 95% confidence interval [CI] 1.12−3.00, I2 = 98.4%, p < .001; plasma: SMD 3.67, 95% CI 2.32−5.03, I2 = 86.0%, p < .001). Subgroup analysis indicated that asthma adults showed higher IL‐33 level in serum, compared to HCs, whereas no significant difference in IL‐33 level in serum was showed between asthma children and HCs (adults: SMD 2.17, 95% CI 1.09−3.25; children: SMD 1.81, 95% CI −0.11 to 3.74). The study indicated that moderate and severe asthmatics showed higher IL‐33 level in serum, compared to mild asthmatics (SMD 0.78, 95% CI 0.41−1.16, I2 = 66.2%, p = .011). Conclusions In conclusion, the main findings of present meta‐analysis suggested that there was a significant correlation between IL‐33 levels and the severity of asthma. Therefore, IL‐33 levels of either serum or plasma may be regarded as a useful biomarker of asthma or the degree of disease. In conclusion, the main findings of present meta‐analysis suggested that there was significant correlation between interleukin (IL)‐33 levels and the severity of asthma. Therefore, the IL‐33 levels of either serum or plasma may be regarded as a useful biomarker of asthma or the degree of disease. However, we can not ignore the influences of ethnic and age factors on the IL‐33 levels. It is encouraged that data from multi‐center, well‐designed and large sample size studies should be conducted for validating the clinical value of IL‐33 on asthma.