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

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 (R), 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 x 10(9)/l to 0.14 +/- 0.04 x 10(9)/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..