Comparison of fluticasone propionate on acute-murine ovalbumin and influenza A-induced airway inflammation

Zakky Cholisoh, Kenneth Broadley, William Ford, Emma Kidd. Cardiff University, Cardiff, UK

Both asthma and respiratory viral infection are the leading cause of airway inflammation. While the roles of corticosteroids are established in asthma, their roles in respiratory viral infection are still controversial1,2. This study aimed to characterize and compare the efficacy of fluticasone propionate (FP) in asthmatic-derived inflammation with viral-induced inflammation

Male BALB/c mice were sensitised with 50 µg ovalbumin (OVA) and 50 mg Al(OH)3 on day 0 and 5 (OVA groups). Influenza A (FLU) infected mice were injected with saline at the respective time points. On day 12, mice were treated with FP (0.25 mg/ml or 0.5 mg/ml dissolved in saline (40%), DMSO (30%) and ethanol (30%) twice daily for 20 minutes, 6 hours apart, aerosol inhalation) for 6 days. FLU group were only treated with the highest dose of FP. Control mice were given the respective vehicle inhalation. On day 13, FLU groups were instilled with H1N1/PR8 (10pfu, 50µl, i.n) or PBS. On day 17, OVA groups were challenged with 0.5% OVA aerosol in saline for 1 hour twice 4 hours apart. On days 11 and 18, mice were observed for airway responsiveness (AR) by increasing doses of inhaled methacholine provocation. Airways responses on day 11, 17, and 18 were measured as Penh (Buxco Systems, USA). On the last day (day 18) mice were culled and broncholaveolar lavage (BAL) was performed to evaluate inflammatory cell influx into the airways. Data was analysed using One-way Analysis of Variance followed by a Bonferroni post-test or unpaired t-test (p<0.05).

OVA challenge led to early asthmatic responses (EAR, 36.2±8.1% ↑ in Penh) which were unaffected by FP, while late asthmatic responses (LAR) measured as the 6-12h peak (46.8±9.6%) were reduced significantly by FP 0.5 mg/ml to 22.3±6.0%. AR significantly increased 24 hours after OVA challenge (absolute Penh 7.1±0.8) compared to pre-OVA value (absolute Penh 1.9±0.3). FP 0.5 mg/ml reduced AR in OVA challenged group to 2.7±0.3 (absolute Penh). FP 0.25 mg/ml did not significantly attenuate either LAR or AR in OVA group. FLU infection also increased AR (absolute Penh 8.8±0.8) which was unaffected by FP. OVA challenge caused eosinophilia and increased total cells (15.1±1.4x105cells/ml) from saline challenged mice (3.1±0.3x105cells/ml). FP 0.25 or 0.5 mg/ml reduced total cell significantly to 8.9±1.7.105cells/ml and 4.6±0.7.105cells/ml respectively. Eosinophil influx as a hallmark of asthma was also significantly reduced by 0.5 mg/ml FP from 6.6±0.6x105cells/ml to 0.6±0.3.105cells/ml. FLU infection led to a marked neutrophilia with an elevation of total cells counts 6.9±0.6x105cells/ml compared to PBS instilled animals 2.1±0.5x105cells/ml which did not reduced by FP.

The study demonstrated that OVA induced allergic airway inflammation was significantly attenuated by FP in dose dependent manner, whereas an effective dose of FP did not exhibit the anti-inflammatory effect on influenza virus infection.

1. Annane, Am J Respir Crit Care Med. 2011;183(9):1125-6

2. Matthay and Liu, Am J Respir Crit Care Med. 2011;183(9):1127-8