Budesonide and formoterol inhibit inflammatory mediator production by bronchial epithelial cells infected with rhinovirus
Open accessAbstract
Summary: Background Rhinoviruses (RVs) are responsible for the majority of acute asthma and chronic obstructive pulmonary disease (COPD) exacerbations. RVs infect the lower airways and induce the production of pro‐inflammatory and remodelling‐associated mediators. Budesonide (BUD) and formoterol (FORM) synergize in controlling asthma and COPD exacerbations; however, their effects on virus‐induced inflammation and remodelling are less known. Objective We investigated whether BUD and FORM synergize in suppressing RV‐induced inflammation and remodelling in the airways. Methods In vitro models of RV infection of BEAS‐2B and primary normal human bronchial epithelial (NHBE) cells were used. We assessed the effects of individual and combined drugs administered post‐infection, at a clinically relevant concentration range (10−6–10−10 m), on the production of CCL5, CXCL10, CXCL8, IL‐6 and the remodelling‐associated VEGF and bFGF, using ELISA and RT‐PCR. Results BUD effectively suppressed RV‐mediated induction of all mediators studied, in a concentration‐dependent manner. FORM alone suppressed the production of CXCL8 and bFGF. The combination of BUD and FORM had concentration‐dependent, additive or synergistic effects in the suppression of RV‐induced CCL5, CXCL8 and CXCL10 in both cell types as well as VEGF in NHBE only. Combination treatment also resulted in an enhanced suppression of RV‐induced IL‐6, and CCL5 at the mRNA level as compared with BUD or FORM alone. Conclusion BUD and FORM suppress RV‐induced chemokines and growth factors in bronchial epithelial cells in a concentration‐dependent, synergistic or additive manner. These data further support the combined use of BUD and FORM in asthma and COPD and intensification of this therapy during exacerbations.
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Many clinical studies have identified positive associations between levels of airway epithelial cell-derived inflammatory mediators and disease severity.
“Many clinical studies have identified positive associations between levels of airway epithelial cell-derived inflammatory mediators and disease severity.”
From The airway epithelium: soldier in the fight against respiratory viruses (2011) · cites this paper as [271]
Dose-related associations were found between several cytokines and chemokines (including IL-8/CXLC8, MIP-1α/CCL3, MCP-1/CCL2, and the IL-6/TNF-α ratio) in respiratory secretions and the severity of RSV bronchiolitis.
“For instance, dose-related associations were found between several cytokines and chemokines (including IL-8/CXLC8, MIP-1α/CCL3, MCP-1/CCL2, and the IL-6/TNF-α ratio) in respiratory secretions and the severity of RSV bronchiolitis (76, 114, 271)”
From The airway epithelium: soldier in the fight against respiratory viruses (2011) · cites this paper as [271]
The associations between inflammatory mediators and RSV bronchiolitis severity suggest a relationship between overly aggressive innate immune responses and disease following infection.
“suggesting a relationship between overly aggressive innate immune responses and disease following infection.”
From The airway epithelium: soldier in the fight against respiratory viruses (2011) · cites this paper as [271]
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The airway epithelium: soldier in the fight against respiratory viruses
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- Authors
- Skevaki, C. L., Christodoulou, I., Spyridaki, I. S., Tiniakou, I., Georgiou, V., Xepapadaki, P., Kafetzis, D. A., & Papadopoulos, N. G.
- Affiliations
- National and Kapodistrian University of Athens (GR)
- Corresponding author
- Skevaki, C. L.
- Venue
- Clinical & Experimental Allergy
- Publisher
- Wiley
- Published
- 2009-10-21
- Volume
- 39
- Issue
- 11
- Pages
- 1700-1710
- ISSN
- 0954-7894 (ISSN-L)
- 1365-2222
- OpenAlex
- W2160971027
- Cited by
- 67
- References
- 36
- Citations by year
- 2026: 2 · 2025: 3 · 2023: 4 · 2022: 6 · 2021: 3 · 2020: 5 · 2019: 1 · 2018: 2 · 2017: 3 · 2016: 3 · 2015: 4 · 2014: 10 · 2013: 7 · 2012: 5
- FWCI
- 3.09
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Licence
- Locations
- Clinical & Experimental Allergy (publishedVersion)
- PubMed (publishedVersion)
- Research Explorer (The University of Manchester) (publishedVersion)
- DSpace - NTUA (National Technical University of Athens) (submittedVersion, other-oa)
- Funders
- AstraZeneca
- European Society for Paediatric Infectious Diseases
- Topics
- Health Sciences › Medicine › Physiology › Asthma and respiratory diseases
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Chronic Obstructive Pulmonary Disease (COPD) Research
- Health Sciences › Medicine › Epidemiology › Respiratory viral infections research
- Keywords
- budesonide, formoterol, rhinovirus infection, bronchial epithelial cells, airway inflammation, airway remodeling, chemokines, RANTES, CXCL10, interleukin-8, interleukin-6, vascular endothelial growth factor, basic fibroblast growth factor, combination therapy, asthma exacerbations, COPD exacerbations, BEAS-2B cells
- MeSH terms
- Formoterol Fumarate, Asthma, Bronchi, Bronchodilator Agents, Drug Synergism, Epithelial Cells, Ethanolamines, Humans, Inflammation, Picornaviridae Infections, Rhinovirus, Fibroblast Growth Factor 2, Intercellular Adhesion Molecule-1, Inflammation Mediators, Chemokines, Budesonide, Respiratory Mucosa, Pulmonary Disease, Chronic Obstructive, Vascular Endothelial Growth Factor A, Chemokine CXCL10
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