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.
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.
Authors: H W Chu; C M Lloyd; W Karmaus; P Maestrelli; P Mason; G Salcedo; J Thaikoottathil; A J Wardlaw Journal: Clin Exp Allergy Date: 2010-11 Impact factor: 5.018
Authors: Sameer K Mathur; Paul S Fichtinger; John T Kelly; Wai-Ming Lee; James E Gern; Nizar N Jarjour Journal: Ann Allergy Asthma Immunol Date: 2013-07 Impact factor: 6.347