Randomized , Double-Blind , Placebo-Controlled , Dose-Escalating Study of Aerosolized Interferon Gamma-1 b in Patients With Mild to Moderate Cystic Fibrosis Lung Disease
Interferon gamma-1b (IFN-g1b) 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, FEV1 40% predicted) were randomly assigned to sequential dose cohorts inhaling 500 mg IFN-g1b, 1,000 mg IFN-g1b, 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 FEV1 of 74 20 (SD)percentpredicted)werestudied.Onepatient hadbronchospasmafter the first doseof IFN-g1b; the overall withdrawal rate was 15% (5 in the placebo group, 2 in the 500-mg IFN-g1b group, and 3 in the 1,000 mg IFN-g1b group). The 500-mg IFN-g1b dose waswell-tolerated, but the 1,000-mg 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, P1⁄40.04), had 24% more hospitalizations for exacerbation than placebo patients (95% CI, 2,45%, P1⁄40.05). There was a 0.12-l difference between the 500-mg IFN-g1b and placebo groups with respect to the