ORIGINAL RESEARCH article
Front. Allergy
Sec. Asthma
Volume 6 - 2025 | doi: 10.3389/falgy.2025.1605109
This article is part of the Research TopicBiologics for Airway Diseases: From bench to bedsideView all articles
Effects of in vitro azithromycin treatment on bronchial epithelial antiviral immunity in asthma phenotypes
Provisionally accepted
Muzhda Ghanizada1
Sofia Malm Tillgren2Louis Praeger-Jahnsen3Nihaya Mahmoud Said1Sisse Ditlev3Helle Frost Andreassen1Nanna Dyhre-Petersen1
Samuel Cerps2Asger Sverrild1Celeste Porsbjerg1
Lena Uller2Therese Lapperre1,4,5
Mandy Menzel2*- 1Respiratory Research Unit, Department of Respiratory and Infectious Diseases, Bispebjerg Hospital, Copenhagen, Denmark
- 2Unit of Respiratory Immunopharmacology, Department of Experimental Medical Science, Lund University, Lund, Sweden
- 3Copenhagen Centre for Translational Research, Copenhagen University Hospital Bispebjerg and Frederiksberg, Copenhagen, Denmark
- 4Department of Respiratory Medicine University Hospital, Antwerp Edegem, Belgium
- 5Laboratory of Experimental Medicine and Paediatrics University of Antwerp, Antwerp Wilrijk, Belgium
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Background: Azithromycin (AZM) effectively reduces asthma exacerbations and enhances bronchial epithelial cell (BEC) antiviral immunity in vitro. However, its clinical impact on different asthma phenotypes is not fully elucidated and differences in treatment response to AZM may be attributable to differences in immune activation to rhinovirus (RV) infection in different inflammatory asthma phenotypes.Objectives: To explore bronchial epithelial antiviral properties in response to in vitro AZM treatment in eosinophilic and non-eosinophilic as well as atopic and non-atopic asthma phenotypes, and to investigate the effects of AZM on the release of RV-induced alarmins and pro-inflammatory cytokines in these asthma phenotypes.In this cross-sectional study, we have collected BECs from patients with moderate-tosevere asthma (n = 20). The cells were pre-treated with or without 10 µM AZM 24 hours before infection with 0.05 MOI RV. Release of IFN-β, IFN-λ, alarmins and pro-inflammatory cytokines were measured 48 hours after infection by Mesoscale Discovery (S-plex and U-plex) and then compared across asthma phenotypes, based on blood eosinophils and atopy status.Results: AZM significantly enhanced IFN-β and IFN-λ protein release in response to RV infection both in eosinophilic and in non-eosinophilic asthma as well as in non-atopic asthma. A less pronounced IFN-β and IFN-λ protein release was also observed in the atopic group. AZM's interferon-inducing effect was, however, largely similar regardless of blood eosinophil count and atopy status. Additionally, AZM prompted the release of TSLP and IL-6 in the non-eosinophilic group only.Our data suggest that in vitro, AZM works primarily by improving bronchial epithelial antiviral resistance by increasing interferons independent of eosinophilia and atopy status,
Keywords: asthma exacerbation, antiviral immunity, Atopy, Rhinovirus, Bronchial epithelial cell, azithromycin (AZM)
Received: 02 Apr 2025; Accepted: 26 May 2025.
Copyright: © 2025 Ghanizada, Malm Tillgren, Praeger-Jahnsen, Said, Ditlev, Frost Andreassen, Dyhre-Petersen, Cerps, Sverrild, Porsbjerg, Uller, Lapperre and Menzel. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Mandy Menzel, Unit of Respiratory Immunopharmacology, Department of Experimental Medical Science, Lund University, Lund, Sweden
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