Budesonide and formoterol inhibit inflammatory mediator production by bronchial epithelial cells infected with rhinovirus.
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.


CONCLUSIONS
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.
Skevaki
C L
CL
Second Department of Pediatrics, Allergy Research Center, University of Athens, Athens, Greece. cskevaki@allergy.gr
Christodoulou
I
I
Spyridaki
I S
IS
Tiniakou
I
I
Georgiou
V
V
Xepapadaki
P
P
Kafetzis
D A
DA
Papadopoulos
N G
NG
D001249:Asthma / Q000188:drug therapy / Q000378:metabolism; D001980:Bronchi / Q000378:metabolism* / Q000821:virology; D001993:Bronchodilator Agents / Q000819:agonists / Q000494:pharmacology* / Q000627:therapeutic use; D019819:Budesonide / Q000819:agonists / Q000494:pharmacology* / Q000627:therapeutic use; D054357:Chemokine CXCL10 / Q000096:biosynthesis; D018925:Chemokines / Q000096:biosynthesis; D004357:Drug Synergism; D004847:Epithelial Cells / Q000378:metabolism* / Q000821:virology; D004983:Ethanolamines / Q000819:agonists / Q000494:pharmacology* / Q000627:therapeutic use; D016222:Fibroblast Growth Factor 2 / Q000096:biosynthesis; D000068759:Formoterol Fumarate; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism*; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D010850:Picornaviridae Infections / Q000188:drug therapy* / Q000378:metabolism; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy / Q000378:metabolism; D020545:Respiratory Mucosa / Q000378:metabolism* / Q000821:virology; D012229:Rhinovirus; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis
D001993:Bronchodilator Agents; C114753:CXCL10 protein, human; D054357:Chemokine CXCL10; D018925:Chemokines; D004983:Ethanolamines; D018836:Inflammation Mediators; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; D018799:Intercellular Adhesion Molecule-1; D019819:Budesonide; D000068759:Formoterol Fumarate