Serum levels of epithelial‐derived mediators and interleukin‐4/interleukin‐13 signaling after bronchial challenge with Dermatophagoides pteronyssinus in patients with allergic asthma

Abstract

Allergens are the main trigger that enhances airway type 2 inflammation, and the epithelium is the first line of defense that reacts to its exposure. Therefore, epithelial‐derived mediators, such as interleukin (IL)‐25, IL‐33, thymic stromal lymphopoietin (TSLP) and ezrin, may play a role as alarmins in IL‐4/IL‐13 signaling in allergic asthma (AA). We investigated the serum levels of IL‐25, IL‐33, TSLP, ezrin, IL‐4 and IL‐13, after bronchial challenge with Dermatophagoides pteronyssinus in patients with AA. We examined 18 subjects: nine steroid‐free stable patients with AA sensitized to D. pteronyssinus and nine non‐atopic healthy subjects (HS). Bronchial allergen challenge was performed using inhaled D. pteronyssinus allergen. IL‐4, IL‐13, IL‐25, IL‐33, TSLP and ezrin levels in serum were measured by ELISA at two time points ‐ before and 24 hours after bronchial allergen challenge. The serum levels of IL‐25, TSLP and ezrin did not differ between AA and HS groups at baseline. However, after allergen exposure, significant increases in serum levels of IL‐25, TSLP and ezrin were observed only in patients with AA. The serum level of IL‐33 at baseline was significantly higher in the AA group compared with HS, but the allergen challenge did not provoke an increase of this cytokine in any group. IL‐4 and IL‐13 levels were significantly higher at baseline in the AA group compared with HS and, after allergen exposure, were significantly increased in the AA group, with no effect on HS. Thus, the epithelial‐derived mediators IL‐25, TSLP and ezrin, via IL4/IL13 signaling, enhance type 2 inflammation after bronchial challenge with D. pteronyssinus in AA.

Stable and exacerbation period serum cytokine and periostin levels of the five distinct phenotypes of severe asthma

“…Peripheral eosinophil counts were particularly high in this study and as for IL-13, peripheral eosinophilia was also correlated with disease severity. Kalinauskaite-Zukauske et al reported a significantly higher IL-13 levels in atopic asthma patients compared to the control group and an increase in IL-13 levels after bronchial allergen challenge test with D. pteronyssinus (18). Basal peripheral eosinophil counts were nearly twice the control group in atopic asthmatic patients in this study.…”

“…The authors also stated that there was no difference in these two cytokines when controlled and uncontrolled asthma patients were compared. In another study, where baseline IL-25 and TSLP levels were similar between atopic asthmatic patients and control group, a significant increase in these two cytokine levels was observed after bronchial inhaler challenge (18). In our study, IL-25 and TSLP was not detected in the serum of phenotype 2 patients in which none of the patients were under long term systemic steroid therapy.…”

“…IL-4 and IL-13 are both potent inducers of VCAM-1in endothelial cells, which are important for the recruitment of eosinophils (13). Relationship between serum IL-13 levels and atopiceosinophilic asthma has been reported in previous studies (16)(17)(18)(19). Hussein et al showed a higher serum IL-13 levels in children with atopic asthma compared to control group and correlation between serum IL-13 levels and disease severity (17).…”

Mechanisms and biomarkers of airway epithelial cell damage in asthma: A review

“…91 In contrast, acute bronchial challenge of patients with steroidnaïve mild allergic asthma with Dermatophagoides pteronyssinus resulted in enhanced serum levels of ezrin and IL-13 after 24 hours. 92 The authors suggested that acute asthma attacks result in heightened release of biologically active substances such as ezrin from damaged AECs, which initiates an IL-13-driven immune cascade that results in further increases in ezrin levels. 92 Further studies are required to look at temporal changes in ezrin levels in various biosamples and the impact of natural asthma exacerbations.…”

“…92 The authors suggested that acute asthma attacks result in heightened release of biologically active substances such as ezrin from damaged AECs, which initiates an IL-13-driven immune cascade that results in further increases in ezrin levels. 92 Further studies are required to look at temporal changes in ezrin levels in various biosamples and the impact of natural asthma exacerbations. Chitinase-3-like protein 1 (CHI3L1), also known as YKL40, is expressed and secreted by various cells such as epithelial cells, macrophages, neutrophils and smooth muscle cells.…”