fluticasone-propionate--salmeterol-xinafoate-drug-combination and Respiratory-Syncytial-Virus-Infections

Airway viral infections provoke exacerbations of asthma and chronic obstructive pulmonary disease. B7-H1 is a costimulatory molecule that is implicated in an escape mechanism of viruses from host immune systems. This escape may be associated with the persistence of viral infection and lead to exacerbation of underlying diseases. We have shown that an analog of viral double-stranded RNA, polyinosinic-polycytidylic acid (poly IC), upregulated the expression of B7-H1 on airway epithelial cells, an effect which was corticosteroid-resistant. We investigated the effects of corticosteroids plus long-acting β(2)-agonists (LABAs; fluticasone/salmeterol or budesonide/formoterol) on the expression of B7-H1.. BEAS-2B cells and primary airway epithelial cells were stimulated with poly IC or respiratory syncytial virus. The expression of B7-H1 was assessed by flow cytometry.. Poly IC upregulated the expression of B7-H1, which was suppressed by high-concentration corticosteroids but not by LABAs. The upregulation was suppressed by very low-concentration corticosteroids when used in combination with LABAs. Their combination also suppressed the virus-induced upregulation of B7-H1. Poly IC stimulation induced the nuclear translocation of nuclear factor ĸB (NF-ĸB). Inhibitors of NF-ĸB activation prevented the poly IC-induced upregulation of B7-H1. Low-concentration corticosteroids in combination with LABAs enhanced the de novo induction of IĸBα, the endogenous inhibitor of NF-ĸB activation.. Fluticasone/salmeterol or budesonide/formoterol attenuate the virus-associated upregulation of B7-H1 on airway epithelial cells via suppression of NF-ĸB activation.

Topics: Adrenal Cortex Hormones; Adrenergic beta-2 Receptor Agonists; Albuterol; Androstadienes; B7-H1 Antigen; Budesonide; Cell Line; Drug Combinations; Ethanolamines; Fluticasone-Salmeterol Drug Combination; Formoterol Fumarate; Humans; I-kappa B Proteins; NF-kappa B; NF-KappaB Inhibitor alpha; Poly I-C; Respiratory Mucosa; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses; Up-Regulation

Respiratory syncytial virus (RSV) infection is the major cause of bronchiolitis in infants and is a risk factor for the development of asthma. Allergic asthmatics are more susceptible to RSV infection and viral exacerbation.. Since the effectiveness of corticosteroids in treating RSV infection has been controversial, we tested fluticasone propionate (FP) and salmeterol (Sal) alone versus FP plus Sal (FPS) on RSV-induced airway inflammation. Mice were sensitized and challenged with ovalbumin (OVA) and infected with RSV. Following infection they were treated with FP, Sal, or FPS intranasally and airway hyperreactivity (AHR), inflammation and RSV titers were examined.. The group treated with FPS showed significantly lower AHR compared to the group treated with FP or Sal alone. The group treated with FP alone showed slightly decreased (non-significant) AHR compared to controls. Treatment with FPS resulted in significant decreases in the percentage of eosinophils and neutrophils in bronchoalveolar lavage fluid and in lung pathology compared to FP or Sal. FP alone decreased eosinophils but not neutrophils or lymphocytes, while Sal alone decreased eosinophils and neutrophils but not lymphocytes. FPS treatment of mice infected with RSV in the absence of allergen sensitization resulted in a 50% decrease of RSV titer in the lung and a reduction in neutrophils compared to FP or Sal.. Together, these results indicate that fluticasone in combination with salmeterol is a more effective treatment for decreasing airway hyperreactivity and inflammation than either of them alone in allergen-sensitized, RSV-infected mice.

Topics: Albuterol; Allergens; Androstadienes; Animals; Anti-Allergic Agents; Asthma; Bronchoalveolar Lavage; Bronchodilator Agents; Drug Combinations; Female; Fluticasone; Fluticasone-Salmeterol Drug Combination; Lung; Mice; Mice, Inbred BALB C; Ovalbumin; Respiratory Syncytial Virus Infections; Salmeterol Xinafoate