Serum Levels of Epithelial-Derived Cytokines as Interleukin-25 and Thymic Stromal Lymphopoietin after a Single Dose of Mepolizumab in Patients with Severe Non-Allergic Eosinophilic Asthma: A Short Report.

Virginija Kalinauskaite-Zukauske,Andrius Januskevicius,Ieva Janulaityte,Kestutis Malakauskas,Skaidrius Miliauskas

doi:10.1155/2019/8607657

Virginija Kalinauskaite-Zukauske, Andrius Januskevicius + Show 3 more

Open Access

https://doi.org/10.1155/2019/8607657

Copy DOI

Abstract

The bronchial epithelium has continuous contact with environmental agents initiating and maintaining airway type 2 inflammation in asthma. However, there is a lack of data on whether reduced airway eosinophilic inflammation can affect the production of epithelial-derived mediators, such as interleukin-25 (IL-25) and thymic stromal lymphopoietin (TSLP). The aim of this study was to investigate the changes in serum levels of IL-25 and TSLP after a single dose of mepolizumab, a humanized monoclonal antibody to interleukin-5 (IL-5), in patients with severe non-allergic eosinophilic asthma (SNEA). We examined 9 SNEA patients before and four weeks after administration of 100 mg mepolizumab subcutaneously. The fractional exhaled nitric oxide (FeNO) level was analysed using an electrochemical assay (NIOX VERO®, Circassia, UK). Serum IL-25 and TSLP levels were measured by ELISA. Four weeks after the single dose of mepolizumab, blood eosinophil count significantly decreased from 0.55 ± 0.20 × 109/l to 0.14 ± 0.04 × 109/l (p = 0.01) and FEV1 increased from 2.1 ± 0.5 l (65.4 ± 8.8% of predicted) to 2.6 ± 0.4 l (76.4 ± 9.1% of predicted) (p = 0.04), while FeNO level has not changed (32.3 ± 8.4 vs 42.9 ± 12.6 ppb). Serum IL-25 level significantly decreased from 48.0 ± 17.2 pg/mL to 34.8 ± 17.1 pg/mL (p = 0.02) with same tendency in TSLP level: from 359.8 ± 71.3 pg/mL to 275.6 ± 47.8 pg/mL (p = 0.02). It has also been noticed a significant relation between changes in the blood eosinophil count and serum IL-25 level (r = 0.81, p = 0.008), as well as between changes in serum IL-25 and TSLP levels (r = 0.93, p = 0.004) after a single dose of mepolizumab. Thus, anti-IL-5 treatment with mepolizumab might diminish the production of bronchial epithelial-derived cytokines IL-25 and TSLP in patients with SNEA which is potentially related to reduced eosinophilic inflammation. This trial is registered in ClinicalTrial.gov with identifier NCT03388359.

Highlights

Asthma is a common, life-lasting airway disease, associated with a high social and economic burden
The initial immune response to inhaled air pollutants or other external triggers occurs already in the bronchial epithelium [11,12,13,14,15,16]. erefore, dysfunction of epithelial cells is becoming an increasingly important part of the pathogenesis of asthma. ere are data that cytokines interleukin- 25 (IL-25) and thymic stromal lymphopoietin (TSLP) are some of the major airway type 2 inflammation regulators derived from the bronchial epithelium [14, 17]. ese cytokines have been described as epithelial-derived alarmins that activate and potentiate the inner immune cascade, including airway eosinophilic inflammation, in the presence of actual damage [14, 16,17,18]
≥0.30 × 109/l blood eosinophil count in the 12-month period before the screening denying other possible common causes of eosinophilia; no other reasons that could lead to poor control of asthma symptoms; documented at least 12-month treatment of high doses of inhaled steroids combined with long-acting beta-agonist ± long-acting antimuscarinic agent ± episodic use of oral steroids prior to inclusion in the study; and in the 12 months before the screening visit ≥2 exacerbations of asthma that required treatment with systemic steroids

Summary

Introduction

Life-lasting airway disease, associated with a high social and economic burden. About 3–8% of all asthma patients have severe asthma, suffering from frequent symptoms and recurrent exacerbations despite the combined treatment with high-dose of inhaled steroids and longacting bronchodilators, often supplemented with oral steroids [1, 2]. All this leads to a significant loss of life quality and labour productivity, increased mortality risk [3, 4]. Canadian Respiratory Journal activation, eosinophils synthesize a row of cytokines, chemokines, growth factors, and other eosinophil-derived proinflammatory products, and all of them contribute to the airway inflammation in asthma, including airway epithelial cell damage, airway dysfunction, and remodeling [7,8,9]. The initial immune response to inhaled air pollutants or other external triggers occurs already in the bronchial epithelium [11,12,13,14,15,16]. erefore, dysfunction of epithelial cells is becoming an increasingly important part of the pathogenesis of asthma. ere are data that cytokines interleukin- 25 (IL-25) and thymic stromal lymphopoietin (TSLP) are some of the major airway type 2 inflammation regulators derived from the bronchial epithelium [14, 17]. ese cytokines have been described as epithelial-derived alarmins that activate and potentiate the inner immune cascade, including airway eosinophilic inflammation, in the presence of actual damage [14, 16,17,18]

Methods

Results

Discussion

Conclusion