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

Abstract EN

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-κB-) dependent inflammation.

NF-κB may also be important in RV replication as inhibition of NF-κB inhibits replication of other viruses such as human immunodeficiency virus and cytomegalovirus.

To establish the role of NF-κB inhibitors in RV-induced IL- 6 and IL-8 and RV replication, we used pharmacological inhibitors of NF-κB, and steroids and/or β2 agonists were used for comparison.

Primary human lung fibroblasts were infected with RV-16 in the presence of NF-κB inhibitors: BAY-117085 and dimethyl fumarate; β2 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-κB 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-κB alone is unlikely to be an effective treatment compared to current asthma therapeutics.