Background: Respiratory Syncytial Virus (RSV) is a problematic respiratory virus responsible for significant morbidity worldwide; particularly in infants, the elderly and those with pre-existing respiratory conditions such as asthma and COPD. Current treatment regimens generally involve the administration of corticosteroids and long-acting beta adrenoceptor agonists which, when administered together, exhibit an evidently synergistic anti-inflammatory and therapeutic effect. The precise cellular mechanisms underpinning the synergy remain unclear, however.
Experimental Approach: This study examined the cellular effects of RSV infection and of the administration of the glucocorticoid, dexamethasone, and the long-acting β adrenoceptor agonist (LABA), salmeterol, both alone and in combination, and temporally relative to RSV infection, by analysing the levels of expression of several inflammation-associated cellular and viral genes in bronchial endothelial cell lines in vitro.
Key Results: The administration of both drugs produced a notable change in the level of expression of a number of inflammation-associated genes. A clear synergy in the effects of the two drugs in combination was noted in the case of two genes: glucocorticoid-induced glycine zipper (GILZ) and mitogen-activated protein kinase phosphatase (MKP). Both genes are well characterised as exerting an anti-inflammatory effect through the suppression of pro-inflammatory elements of intracellular signalling cascades.
Conclusions and Implications: The confirmation that both GILZ and MKP are upregulated in the case of combination glucocorticoid and LABA therapy and that an evident synergy exists between the two drugs elucidates a potentially significant mechanistic step in the anti-inflammatory effects of the two drugs. Although their enhanced combinatorial effects have been noted previously, a quantitative assessment of the effects of their combined administration in the case of RSV infection may assist efforts to understand the precise cellular effects of these, or similar drugs, and efforts to develop clinically significant patient outcome improvements in cases of RSV infection.
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