Title :

Mepolizumab Attenuates Airway Eosinophil Numbers, but Not Their Functional Phenotype, in Asthma.

Author(s) :

Kelly, Elizabeth A [Auteur]
Esnault, Stéphane [Auteur]
University of Wisconsin School of Medicine and Public Health
Liu, Lin Ying [Auteur]
Evans, Michael D [Auteur]
Johansson, Mats W [Auteur]
Mathur, Sameer [Auteur]
Mosher, Deane F [Auteur]
Denlinger, Loren C [Auteur]
Jarjour, Nizar N [Auteur]

Journal title :

American Journal of Respiratory and Critical Care Medicine

Abbreviated title :

Am J Respir Crit Care Med

Volume number :

196

Pages :

1385-1395

Publication date :

2017-12-01

ISSN :

1535-4970

English keyword(s) :

Adult
Antibodies, Monoclonal, Humanized
Asthma
Biopsy
Bronchi
Bronchoalveolar Lavage Fluid
Enzyme-Linked Immunosorbent Assay
Eosinophils
Flow Cytometry
Humans
Male
Phenotype
Polymerase Chain Reaction
Respiratory System
IL-3 receptor
IL-5
allergen challenge

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

Mepolizumab, an IL-5-blocking antibody, reduces exacerbations in patients with severe eosinophilic asthma. Mepolizumab arrests eosinophil maturation; however, the functional phenotype of eosinophils that persist in the ...
Show more >Mepolizumab, an IL-5-blocking antibody, reduces exacerbations in patients with severe eosinophilic asthma. Mepolizumab arrests eosinophil maturation; however, the functional phenotype of eosinophils that persist in the blood and airway after administration of IL-5 neutralizing antibodies has not been reported. To determine the effect of anti-IL-5 antibody on the numbers and phenotypes of allergen-induced circulating and airway eosinophils. Airway inflammation was elicited in participants with mild allergic asthma by segmental allergen challenge before and 1 month after a single intravenous 750-mg dose of mepolizumab. Eosinophils were examined in blood, bronchoalveolar lavage, and endobronchial biopsies 48 hours after challenge. Segmental challenge without mepolizumab induced a rise in circulating eosinophils, bronchoalveolar lavage eosinophilia, and eosinophil peroxidase deposition in bronchial mucosa. IL-5 neutralization before allergen challenge abolished the allergen-induced rise in circulating eosinophils and expression of IL-3 receptors, whereas airway eosinophilia and eosinophil peroxidase deposition were blunted but not eliminated. Before mepolizumab treatment, bronchoalveolar lavage eosinophils had more surface IL-3 and granulocyte-monocyte colony-stimulating factor receptors, CD69, CD44, and CD23 and decreased IL-5 and eotaxin receptors than blood eosinophils. This activation phenotype indicated by bronchoalveolar lavage eosinophil surface markers, as well as the release of eosinophil peroxidase by eosinophils in the bronchial mucosa, was maintained after mepolizumab. Mepolizumab reduced airway eosinophil numbers but had a limited effect on airway eosinophil activation markers, suggesting that these cells retain functionality. This observation may explain why IL-5 neutralization reduces but does not completely eradicate asthma exacerbations. Clinical trial registered with www.clinicaltrials.gov (NCT00802438).Show less >

Language :

Anglais

Peer reviewed article :

Oui

Audience :

Internationale

Popular science :

Non

Administrative institution(s) :

Université de Lille
Inserm
CHU Lille

Collections :

• Autres travaux scientifiques

Submission date :

2023-10-23T11:48:52Z
2024-03-16T08:33:31Z