Effects of β2 Agonists, Corticosteroids, and Novel Therapies on Rhinovirus-Induced Cytokine Release and Rhinovirus Replication in Primary Airway Fibroblasts. (24th October 2011)

• Record Type: Journal Article
• Authors: Van Ly, David; King, Nicholas J.C.; Moir, Lyn M.; Burgess, Janette K.; Black, Judith L.; Oliver, Brian G.
• Other Names: Borger Peter Academic Editor.
• Is Part Of: Journal of allergy. Volume 2011(2011)
• Publication Date: 2011-10-24
• Subjects: Allergy -- Periodicals; Immunologic diseases -- Periodicals; Allergy and Immunology; Hypersensitivity; Immune System Diseases; Allergy; Immunologic diseases; Electronic journals; Periodical; Periodicals; 616.97
• DOI: 10.1155/2011/457169
• Languages: English
• ISSNs: 1687-9783

Abstract

Abstract : 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.