Abstract
Background: Oxidative stress and mitochondrial dysfunction are enhanced in severe asthma yet their role during viral-induced asthma exacerbations (AEs) remains unclear.
Hypothesis: Human rhinovirus (HRV) infections cause AEs by driving an increase in oxidative stress and mitochondrial dysfunction.
Methods: Balb/c mice (n=5 per group) were sensitised with house dust mite (HDM) in an adjuvant suspension and then challenged with HDM at day 14 and 17, before being infected with HRV1b at day 19. Mice were also treated at day 14 and 17 with the mitochondrial targeted antioxidant SS31. Airway hyperresponsiveness (AHR), inflammation, oxidative stress and mitochondrial function were assessed at 12, 24 and 72 hours post infection.
Results: HRV1b exacerbation caused a significant increase in AHR (reduction in –logPC100, Figure), and airway inflammation (total BAL cell counts and inflammatory cytokines). Mitochondrial reactive oxygen species (mtROS), but not mitochondrial membrane potential (ΔΨm), was elevated by HRV1b. SS31 treatment in the asthma and exacerbation model significantly decreased AHR, total BAL cell counts and inflammatory cytokines, without affecting mtROS or ΔΨm.
Conclusion: We generated a novel, reproducible, in vivo viral exacerbation model of asthma. SS31 significantly attenuates key features of an AE in this model. Further work will examine mitochondrial function in the lungs of these animals.
Footnotes
Cite this article as: European Respiratory Journal 2020; 56: Suppl. 64, 4083.
This abstract was presented at the 2020 ERS International Congress, in session “Respiratory viruses in the "pre COVID-19" era”.
This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only).
- Copyright ©the authors 2020
