title: Budesonide and formoterol inhibit inflammatory mediator production by bronchial epithelial cells infected with rhinovirus.
abstract: 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.
authors: Second Department of Pediatrics, Allergy Research Center, University of Athens, Athens, Greece. cskevaki@allergy.gr
authors: C L
authors: CL
authors: Skevaki
authors: I
authors: I
authors: Christodoulou
authors: I S
authors: IS
authors: Spyridaki
authors: I
authors: I
authors: Tiniakou
authors: V
authors: V
authors: Georgiou
authors: P
authors: P
authors: Xepapadaki
authors: D A
authors: DA
authors: Kafetzis
authors: N G
authors: NG
authors: Papadopoulos
mesh_terms: 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
chemical_list: 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