Budesonide and formoterol reduce early innate anti-viral immune responses in vitro

Davies, Janet M., Carroll, Melanie L., Li, Hongzhou, Poh, Alisa M., Kirkegard, Darren, Towers, Michelle and Upham, John W. (2011) Budesonide and formoterol reduce early innate anti-viral immune responses in vitro. PLoS One, 6 11: e27898.1-e27898.8. doi:10.1371/journal.pone.0027898


Author Davies, Janet M.
Carroll, Melanie L.
Li, Hongzhou
Poh, Alisa M.
Kirkegard, Darren
Towers, Michelle
Upham, John W.
Title Budesonide and formoterol reduce early innate anti-viral immune responses in vitro
Journal name PLoS One   Check publisher's open access policy
ISSN 1932-6203
Publication date 2011-11
Sub-type Article (original research)
DOI 10.1371/journal.pone.0027898
Open Access Status DOI
Volume 6
Issue 11
Start page e27898.1
End page e27898.8
Total pages 8
Editor Jacques Zimmer
Place of publication Public Library of Science
Publisher San Francisco, CA, United States
Collection year 2012
Language eng
Formatted abstract
Asthma is a chronic inflammatory airways disease in which respiratory viral infections frequently trigger exacerbations. Current treatment of asthma with combinations of inhaled corticosteroids and long acting beta2 agonists improves asthma control and reduces exacerbations but what impact this might have on innate anti-viral immunity is unclear. We investigated the in vitro effects of asthma drugs on innate anti-viral immunity. Peripheral blood mononuclear cells (PBMC) from healthy and asthmatic donors were cultured for 24 hours with the Toll-like receptor 7 agonist, imiquimod, or rhinovirus 16 (RV16) in the presence of budesonide and/or formoterol. Production of proinflammatory cytokines and expression of anti-viral intracellular signalling molecules were measured by ELISA and RT-PCR respectively. In PBMC from healthy donors, budesonide alone inhibited IP-10 and IL-6 production induced by imiquimod in a concentration-dependent manner and the degree of inhibition was amplified when budesonide and formoterol were used in combination. Formoterol alone had little effect on these parameters, except at high concentrations (10-6 M) when IL-6 production increased. In RV16 stimulated PBMC, the combination of budesonide and formoterol inhibited IFNa and IP-10 production in asthmatic as well as healthy donors. Combination of budesonide and formoterol also inhibited RV16-stimulated expression of the type I IFN induced genes myxovirus protein A and 2', 5' oligoadenylate synthetise. Notably, RV16 stimulated lower levels of type Myxovirus A and oligoadenylate synthase in PBMC of asthmatics than control donors. These in vitro studies demonstrate that combinations of drugs commonly used in asthma therapy inhibit both early pro-inflammatory cytokines and key aspects of the type I IFN pathway. These findings suggest that budesonide and formoterol curtail excessive inflammation induced by rhinovirus infections in patients with asthma, but whether this inhibits viral clearance in vivo remains to be determined. 
Keyword Bronchial Epithelial Cells
Smooth Muscle Cells
Asthma Exacerbations
Experimental Infection
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2012 Collection
School of Medicine Publications
 
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