The effect of fluticasone propionate on respiratory syncytial virus-induced chemokine release by a human bronchial epithelial cell line.
ABSTRACT Respiratory syncytial virus (RSV) is an important cause of bronchiolitis in infants, is an important trigger of asthma exacerbation, and stimulates chemokine production by human respiratory epithelial cells in vitro. We tested the effect of the corticosteroid fluticasone propionate (FP) on RSV-stimulated production of the chemokines interleukin 8 (IL-8) and RANTES (regulated upon activation, normal T cell expressed and secreted) by a human bronchial epithelial cell line, BEAS-2B. Confluent BEAS-2B cultures were inoculated with RSV at approximately 1 plaque-forming unit/cell, and media were collected at 24 h intervals. Concentrations of IL-8 and RANTES were measured in supernatants using ELISA. The effect of FP at varying concentrations on RSV-induced chemokine release was determined. RSV stimulated increased release of both IL-8 and RANTES, particularly at 24-48 h after virus inoculation. Significant but incomplete inhibition of RSV-stimulated increases for both chemokines was found when cultures were treated with FP at > or = 10(-8) M (for IL-8) or > or = 10(-7) M (for RANTES). There was no significant effect of FP on release of RSV itself from infected BEAS-2B cells. We conclude that a possible mechanism for the efficacy of inhaled corticosteroids in reducing the frequency or severity of asthma exacerbations is inhibition of virus-induced chemokine production by airway cells.
Article: Combined fluticasone propionate and salmeterol reduces RSV infection more effectively than either of them alone in allergen-sensitized mice.[show abstract] [hide abstract]
ABSTRACT: 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.Virology Journal 02/2006; 3:32. · 2.34 Impact Factor
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ABSTRACT: To examine the efficacy of oral dexamethasone in acute bronchiolitis. A double-blind randomized, placebo-controlled trial involving 70 children < 24 months old in the emergency department with Respiratory Disease Assessment Instrument > or = 6. Each patient received either 1 dose of 1 mg/kg of oral dexamethasone or placebo and was assessed hourly for a 4-hour period. Repeated measures regression analysis evaluated a change in the Respiratory Assessment Change Score (RACS). The 2 groups had similar baseline characteristics with Respiratory Disease Assessment Inventory of 9.4 +/- 2.3 in the dexamethasone group (n = 36) and 10.0 +/- 2.7 in the placebo group (n = 34). The RACS was -5.0 +/- 3.1 in the dexamethasone group and -3.2 +/- 3.7 in the placebo group (P =.029). Poor RACS occurred in 41% and 17% of the placebo and dexamethasone groups, respectively (P =.034). Of the children treated with dexamethasone, 19% were hospitalized compared with 44% in the placebo group (P =.039). There was no difference in RACS between the groups on day 7 (P =.75). Outpatients with moderate-to-severe acute bronchiolitis derive significant clinical and hospitalization benefit from oral dexamethasone treatment in the initial 4 hours of therapy.Journal of Pediatrics 01/2002; 140(1):27-32. · 4.11 Impact Factor