Effects of β2 Agonists, Corticosteroids, and Novel Therapies on Rhinovirus-Induced Cytokine Release and Rhinovirus Replication in Primary Airway Fibroblasts

Rhinovirus-(RV-) induced asthma exacerbations account for high asthma-related health costs and morbidity in Australia. The cellular mechanism underlying this pathology is likely the result of RV-induced nuclear-factor-kappa-B-(NF- κ B-) dependent inflammation. NF- κ B may also be important in RV replication as inhibition of NF- κ B inhibits replication of other viruses such as human immunodeficiency virus and cytomegalovirus. To establish the role of NF- κ B inhibitors in RV-induced IL- 6 and IL-8 and RV replication, we used pharmacological inhibitors of NF- κ B, and steroids and/or β 2 agonists were used for comparison. Primary human lung fibroblasts were infected with RV-16 in the presence of NF- κ B inhibitors: BAY-117085 and dimethyl fumarate; β 2 agonist: salmeterol; and/or corticosteroids: dexamethasone; fluticasone. RV-induced IL-6 and IL-8 and RV replication were assessed using ELISAs and virus titration assays. RV replicated and increased IL-6 and IL-8 release. Salmeterol increased, while dexamethasone and fluticasone decreased RV-induced IL-6 and IL-8 ( P<0.05 ). The NF- κ B inhibitor BAY-117085 inhibited only RV-induced IL-6 ( P<0.05 ) and dimethyl fumarate did not alter RV-induced IL-6 and IL-8. Dimethylfumarate increased RV replication whilst other drugs did not alter RV replication. These data suggest that inhibition of NF- κ B alone is unlikely to be an effective treatment compared to current asthma therapeutics.