Immunomodulatory effects of Mepolizumab on group 2 innate lymphoid cells in patients with refractory chronic cough and eosinophilic airways disease (MUCOSA)

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Background: Patients with refractory chronic cough (RCC) secondary to asthma or non-asthmatic eosinophilic bronchitis (NAEB) often have persistent cough despite inhaled or oral corticosteroid. Eosinophils colocalized to airway sensory nerves can increase neuronal sensitivity after allergen challenge1,2. Treatment with mepolizumab, an anti-IL-5 antibody, attenuates airway and blood eosinophilia3. Objective: To assess the effects of mepolizumab on group 2 innate lymphoid cells (ILC2) in patients with RCC. Methods: We conducted a randomized, double-blind, placebo-controlled, parallel-group trial of RCC patients with asthma or NAEB and sputum eosinophilia ≥2%. Patients were randomized 1:1 to receive 4 doses of 100 mg mepolizumab or placebo. Blood ILC2 were phenotyped pre- and post-treatment by flow cytometry and assessed for expression of intracellular cytokine and neuromedin U receptor 1 (NMUR1). Results: Data on 19/30 patients was available for analysis (10 placebo, 9 mepolizumab). Treatment with mepolizumab significantly increased IL-10+ILC2 and NMUR1+IL-10+ILC2 but not total or IL-5/13+ILC2 compared with placebo. In ex-vivo-expanded blood ILC2, co-culture with NMU or IL-33 significantly increased IL-10 intracellular expression in vitro. Conclusions: Mepolizumab treatment increased levels of regulatory ILC2 suggesting an immunomodulatory effect on these cells. erj;66/suppl_69/PA4725/F1 F1 F1

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