Abstract
Introduction: Viral infection is recognised as a cause of exacerbation in asthmatics, and influenza is a seasonal virus that is recognised as contributing in this way, leading to severe and poorly controlled asthma. The objective of this study was to evaluate influenza-induced exacerbation in a house dust mite (HDM) murine model.
Methods: Mice (20-30g, male BalbC) were sensitised with HDM (50 µg, s.c., day 0 and 7) and challenged on day 14 with HDM (10 µg, i.n.). On day 15, mice were infected with influenza A (IAV) (1 x 103 pfu, X31 [H3N2]) or UV-deactivated IAV. Some animals were treated with dexamethasone (DEX, 1-10 mg/kg, QD) on days 14-18. 3 or 4 days after IAV infection, pulmonary inflammation and airway hyper-responsiveness (AHR) were evaluated.
Results: IAV infection in HDM sensitised animals caused a significant (P<0.05) increase in pulmonary inflammation with an increase in neutrophils (0.35 ± 0.13 v 0.03 ± 0.02 x 105 /mL) and eosinophils (4.5 ± 0.49 v 1.7 ± 0.13 x 105 /mL) when compared to animals sensitised to HDM + UV-IAV. This was also associated with a significant increase in AHR to methacholine (50 mg/mL aerosol, total resistance 2814 ± 277 v 1118 ± 117). Treatment with DEX had no significant effect on the HDM + IAV inflammation and AHR which was in contrast to what was observed in HDM sensitised animals.
Conclusion: IAV exacerbates the pulmonary inflammation and AHR seen in HDM sensitised animals with an effect that is steroid in-sensitive. This closely resembles what is seen in man and therefore this model may be useful for the evaluation of novel compounds in the treatment of viral induced exacerbation in asthma.
- Copyright ©the authors 2016