Targeting IL-5 pathway against airway hyperresponsiveness: A comparison between benralizumab and mepolizumab.
IL-5
airway hyperresponsiveness
airway smooth muscle
benralizumab
head to head
mepolizumab
severe asthma
Journal
British journal of pharmacology
ISSN: 1476-5381
Titre abrégé: Br J Pharmacol
Pays: England
ID NLM: 7502536
Informations de publication
Date de publication:
10 2020
10 2020
Historique:
received:
28
04
2020
revised:
14
07
2020
accepted:
10
08
2020
pubmed:
29
8
2020
medline:
22
6
2021
entrez:
29
8
2020
Statut:
ppublish
Résumé
Airway hyperresponsiveness (AHR) is a central abnormality in asthma. IL-5 may modulate AHR in animal models of asthma, but the available data is inconsistent on the impact of targeting IL-5 pathway against AHR. The difference between targeting IL-5 or the IL-5 receptor, α subunit (IL-5Rα) in modulating AHR remains to be investigated in human airways. The aim of this study was to compare the role of the anti-IL-5Rα benralizumab and the anti-IL-5 mepolizumab against AHR and to assess whether these agents influence the levels of cAMP. Passively sensitized human airways were treated with benralizumab and mepolizumab. The primary endpoint was the inhibition of AHR to histamine. The secondary endpoints were the protective effect against AHR to parasympathetic activation and mechanical stress, and the tissue modulation of cAMP. Benralizumab and mepolizumab significantly inhibited the AHR to histamine (maximal effect -134.14 ± 14.93% and -108.29 ± 32.16%, respectively), with benralizumab being 0.73 ± 0.10 logarithm significantly more potent than mepolizumab. Benralizumab and mepolizumab significantly inhibited the AHR to transmural stimulation and mechanical stress. Benralizumab was 0.45 ± 0.16 logarithm significantly more potent than mepolizumab against AHR to parasympathetic activation. The effect of these agents was significantly correlated with increased levels of cAMP. Targeting the IL-5/IL-5Rα axis is an effective strategy to prevent the AHR. Benralizumab was more potent than the mepolizumab and the concentration-dependent beneficial effects of both these monoclonal antibodies were related to improved levels of cAMP in hyperresponsive airways.
Sections du résumé
BACKGROUND AND PURPOSE
Airway hyperresponsiveness (AHR) is a central abnormality in asthma. IL-5 may modulate AHR in animal models of asthma, but the available data is inconsistent on the impact of targeting IL-5 pathway against AHR. The difference between targeting IL-5 or the IL-5 receptor, α subunit (IL-5Rα) in modulating AHR remains to be investigated in human airways. The aim of this study was to compare the role of the anti-IL-5Rα benralizumab and the anti-IL-5 mepolizumab against AHR and to assess whether these agents influence the levels of cAMP.
EXPERIMENTAL APPROACH
Passively sensitized human airways were treated with benralizumab and mepolizumab. The primary endpoint was the inhibition of AHR to histamine. The secondary endpoints were the protective effect against AHR to parasympathetic activation and mechanical stress, and the tissue modulation of cAMP.
KEY RESULTS
Benralizumab and mepolizumab significantly inhibited the AHR to histamine (maximal effect -134.14 ± 14.93% and -108.29 ± 32.16%, respectively), with benralizumab being 0.73 ± 0.10 logarithm significantly more potent than mepolizumab. Benralizumab and mepolizumab significantly inhibited the AHR to transmural stimulation and mechanical stress. Benralizumab was 0.45 ± 0.16 logarithm significantly more potent than mepolizumab against AHR to parasympathetic activation. The effect of these agents was significantly correlated with increased levels of cAMP.
CONCLUSION AND IMPLICATIONS
Targeting the IL-5/IL-5Rα axis is an effective strategy to prevent the AHR. Benralizumab was more potent than the mepolizumab and the concentration-dependent beneficial effects of both these monoclonal antibodies were related to improved levels of cAMP in hyperresponsive airways.
Identifiants
pubmed: 32857420
doi: 10.1111/bph.15240
pmc: PMC7520436
doi:
Substances chimiques
Anti-Asthmatic Agents
0
Antibodies, Monoclonal, Humanized
0
Interleukin-5
0
benralizumab
71492GE1FX
mepolizumab
90Z2UF0E52
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
4750-4765Informations de copyright
© 2020 The British Pharmacological Society.
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