Abstract
Background: Rhinovirus (RV)-induced allergic asthma exacerbations are an important unmet clinical need. Such episodes are characterised by augmented neutrophilic and type 2 inflammation, however mechanistic links between viral infection and ensuing pathophysiology are poorly understood. Granulocyte-colony stimulating factor (G-CSF) is classically recognized as a regulator of neutrophilic inflammation, but we have shown that it can also potentiate type 2 innate lymphoid cell (ILC2) function. Thus, we hypothesised that RV-induced G-CSF drives pathology of asthma exacerbations through concomitantly augmenting neutrophilic and ILC2 responses.
Methods: Healthy controls and asthmatic patients were experimentally inoculated with RV16. Bronchoalveolar lavage and bronchial brushings were collected at baseline and after infection. Subsequently, G-CSF was neutralised in an ovalbumin (OVA)-RV mouse model of asthma exacerbation to assess its capacity to ameliorate pathology.
Results: RV16 infection of asthmatic patients resulted in a significant induction of G-CSF protein and transcript, which correlated with levels of neutrophilia, type 2 inflammation and adverse clinical outcomes. These findings were directly recapitulated in the murine OVA-RV model, whereby subsequent G-CSF neutralisation reduced neutrophilic and ILC2 responses.
Conclusions: G-CSF acts as an instigator of pathophysiology in the context of viral exacerbations of allergic asthma, owing to its capacity to potentiate both neutrophilic and type 2 inflammation. Antibodies targeting G-CSF receptor have completed phase I trials and could represent a new therapeutic strategy for asthma exacerbations.
Footnotes
Cite this article as ERJ Open Research 2022; 8: Suppl. 8, 191.
This article was presented at the 2022 ERS Lung Science Conference, in session “Poster Session 2”.
This is an ERS Lung Science Conference 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 2022