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

Pediatr Pulmonol. 2005 Mar;39(3):209-18. doi: 10.1002/ppul.20152.


Interferon gamma-1b (IFN-gamma1b) is a pleiotropic cytokine with immunomodulatory activities that could decrease bacterial burden, inflammation, and obstruction in patients with CF. Patients with CF (> or =12 years old, FEV1 > or =40% predicted) were randomly assigned to sequential dose cohorts inhaling 500 microg IFN-gamma1b, 1,000 microg IFN-gamma1b, 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) percent predicted) were studied. One patient had bronchospasm after the first dose of IFN-gamma1b; the overall withdrawal rate was 15% (5 in the placebo group, 2 in the 500-microg IFN-gamma1b group, and 3 in the 1,000 microg IFN-gamma1b group). The 500-microg IFN-gamma1b dose was well-tolerated, but the 1,000-mug dose cohort, who had a higher baseline bacterial density than placebo patients (mean difference, 1.2 log(10) 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-microg IFN-gamma1b 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-microg IFN-gamma1b and placebo groups (95% CI, -0.16,0.17, P=0.96). No effects of IFN-gamma1b were seen in sputum bacterial density or inflammatory biomarkers at 12 weeks. Aerosolized IFN-gamma1b did not improve pulmonary function, reduce sputum bacterial density, or affect inflammatory sputum markers in patients with mild-moderate lung disease.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Administration, Inhalation
  • Adolescent
  • Adult
  • Anti-Bacterial Agents / therapeutic use
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / adverse effects
  • Colony Count, Microbial
  • Cystic Fibrosis / classification
  • Cystic Fibrosis / complications*
  • Cystic Fibrosis / drug therapy*
  • Cystic Fibrosis / metabolism
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Administration Schedule
  • Dyspnea / chemically induced
  • Female
  • Hemoptysis / chemically induced
  • Hospitalization
  • Humans
  • Interferon-gamma / administration & dosage*
  • Interferon-gamma / adverse effects
  • Interleukin-8 / analysis
  • Male
  • Neutrophils / metabolism
  • Pancreatic Elastase / analysis
  • Peroxidase / analysis
  • Recombinant Proteins
  • Respiratory Tract Infections / drug therapy*
  • Respiratory Tract Infections / etiology*
  • Respiratory Tract Infections / metabolism
  • Sputum / chemistry
  • Sputum / microbiology
  • Treatment Outcome


  • Anti-Bacterial Agents
  • Antineoplastic Agents
  • Interleukin-8
  • Recombinant Proteins
  • Interferon-gamma
  • Peroxidase
  • Pancreatic Elastase