Do eosinophils contribute to oxidative stress in mild asthma?
Do eosinophils contribute to oxidative stress in mild asthma?
Linsey E.S. de Groot1,2*, Yanaika S. Sabogal Piñeros1,2*, Suzanne M. Bal1,2, Marianne A. van de Pol1, Jörg Hamann2, Peter J. Sterk1, Wim Kulik3 and René Lutter1,2,$
1Department of Respiratory Medicine, 2Department of Experimental Immunology (Amsterdam Infection & Immunity Institute) and 3Laboratory Genetic Metabolic Diseases, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
*These authors contributed equally to this work. $ Presenting author.
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Abstract:
Introduction: Asthma exacerbations are predominantly triggered by respiratory viral infections and characterized by eosinophilic airway inflammation and increased oxidative stress. Eosinophils can produce reactive oxygen species and a link between eosinophils and oxidative stress during exacerbations is thus likely. Attenuation of eosinophils using anti-IL-5 (mepolizumab) in severe asthmatics significantly reduces exacerbation rates and corticosteroid dependency. Here, we aimed to study the contribution of eosinophils to oxidative stress in stable and virus-induced worsening of asthma.
Methods: Mild asthmatics received one high dose of mepolizumab or placebo and after two weeks were subjected to rhinovirus 16 (RV16) infection. Exhaled breath condensate (EBC) and plasma was collected at baseline, after treatment and after RV16 challenge and levels of malondialdehyde (MDA), nitrotyrosine, bromotyrosine, chlorotyrosine and asymmetric dimethylarginine (ADMA) were measured using UPLC-MS/MS and HRMS.
Results: Baseline oxidative stress was not significantly different between the mepolizumab and placebo group and did not change upon treatment. EBC MDA near-significantly and nitrotyrosine significantly increased after virus exposure in the placebo group, but not in the Mepolizumab group. When stratified for patients with high and low eosinophil counts, MDA levels significantly increased in the high eosinophilic placebo group only. No significant differences were observed after RV16 for any of the biomarkers in plasma.
Conclusion: We have demonstrated that in mild asthma eosinophils may contribute to local oxidative stress, but only after RV16-induced loss of asthma control and not in stable disease. This work is supported by the Lung Foundation Netherlands (4.1.15.002 and 3.2.10.069) and GSK (CRT 114696).
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