Randomized, double-blind, placebo-controlled, dose-escalating study of aerosolized interferon gamma-1b in patients with mild to moderate cystic fibrosis lung disease

Interferon gamma-1b (IFN-γ1b) is a pleiotropic cytokine with immunomodulatory activities that could decrease bacterial burden, inflammation, and obstruction in patients with CF Patients with CF (≥12 years old, FEV ₁ ≥40% predicted) were randomly assigned to sequential dose cohorts inhaling 500 μg IFN-γ1b, 1,000 μg IFN-γ1b, or placebo by Respirgard II® nebulizer thrice weekly for 12 weeks. Sputum bacterial density and spirometry were measured. Safety, antibiotic use, hospitalization, and sputum neutrophils, elastase, DNA, IL-8, and myeloperoxidase were also evaluated. Sixty-six patients (mean age, 24 years, with mean baseline FEV ₁ of 74 ± 20 (SD) percent predicted) were studied. One patient had bronchospasm after the first dose of IFN-γ1b; the overall withdrawal rate was 15% (5 in the placebo group, 2 in the 500 μg IFN-γ1b group, and 3 in the 1,000 μg IFN-γ1b group). The 500 μg IFN-γ1b dose was well-tolerated, but the 1,000 μg dose cohort, who had a higher baseline bacterial density than placebo patients (mean difference, 1.2 log₁₀ CFU/g sputum, 95% confidence interval (CI), 0.1, 2.8, P = 0.04), had 24% more hospitalizations for exacerbation than placebo patients (95% CI, 2.45%, P = 0.05). There was a 0.12-l difference between the 500 μg IFN-γ1b and placebo groups with respect to the 12-week change in FEV₁ (active group minus placebo group, 95% CI, -0.03, 0.26, P = 0.11), as compared to a 0.01-l difference between the 1,000-μg IFN-γ1b and placebo groups (95% CI, -0.16, 0.17, P = 0.96). No effects of IFN-γ1b were seen in sputum bacterial density or inflammatory biomarkers at 12 weeks. Aerosolized IFN-γ1b did not improve pulmonary function, reduce sputum bacterial density, or affect inflammatory sputum markers in patients with mild-moderate lung disease.