Antiviral biomarkers are upregulated in sputum cells following administration of inhaled interferon beta to COPD patients

Background: Interferon beta (IFN-β) plays a key role in host defence against viruses, triggering the expression of interferon stimulated genes (ISG) which restrict viral replication and promote antiviral immune responses. Inhaled IFN-β is being developed as a treatment for viral exacerbations of lung disease. In previous studies, treatment with inhaled IFN-β boosted lung antiviral defences (sputum cell ISG expression) and improved lung function and symptoms in ‘difficult-to-treat’ asthmatics with a cold or flu infection (Djukanović AJRCCM 2014 190(2):145-54). SG015 (NCT03570359) is an ongoing study in COPD patients, without (Part 1) and with (Part 2) a confirmed respiratory virus infection, assessing antiviral biomarker responses and clinical effects of inhaled IFN-β compared to placebo. Results from Part 1 are presented. Methods: 10 patients received three daily doses of IFN-β (6MIU) or placebo (8:2 ratio) via a nebuliser. Sputum was collected prior to dosing (baseline), 24hrs post first and third dose and 4-6 days after their third dose. Sputum cell gene expression (Mx1, OAS1, IFIT2, GBP1 and CXCL10) was determined by RT-qPCR. Results: Inhaled IFN-β was well tolerated. All antiviral biomarkers were significantly upregulated 24hrs post dose compared to baseline (p<0.05), except CXCL10 after 3rd dose (p=0.06) (n=5-6). Fold upregulation in Mx1 and OAS1 gene expression was similar to that seen at the same dose in stable asthmatics. Conclusions: Antiviral biomarkers were significantly upregulated in the lungs of COPD patients following the administration of inhaled IFN-β, supporting the proposed mechanism-of-action as a treatment for virus-induced exacerbations.