Delivery and safety of inhaled interferon-γ in idiopathic pulmonary fibrosis

J Aerosol Med Pulm Drug Deliv. 2012 Apr;25(2):79-87. doi: 10.1089/jamp.2011.0919. Epub 2012 Feb 23.


Background: Inhaled interferon-γ aerosol (aINF-γ) may be effective treatment for idiopathic pulmonary fibrosis (IPF). We evaluated safety and delivery of aIFN-γ (100 μg 3 times/week) in 10 IPF patients using the I-neb (Philips Respironics, Parsippany, NJ).

Methods: IFN-γ activity in the aerosol was confirmed by viral inhibition. Ten patients with an average age of 68 diagnosed with IPF (American Thoracic Society/European Respiratory Society consensus guidelines) were enrolled. In vivo deposition was measured via a gamma camera. The nebulizer recorded patient adherence to therapy. Pulmonary function tests [PFTs, forced vital capacity (FVC), total lung capacity (TLC), diffusing capacity for carbon monoxide (DLCO)] and the 6-min walk test were measured at baseline, and every 12-14 weeks for 80 weeks. Bronchoalveolar lavage (BAL) of the middle lobe was performed at baseline and 28 weeks. BAL and plasma samples were analyzed for chemokines and cytokines, including INF-γ.

Results: All 10 patients tolerated 80 weeks of inhaled IFN-γ well, with no systemic side effects. True adherence with aerosol treatment averaged 96.7 ± 4.81% (± SEM). In vivo lung deposition averaged 65.4 ± 4.8μg and oropharyngeal deposition 12.6 ± 3.0 μg. BAL IFN-γ increased 60-fold and profibrotic cytokines (FGP-2, Flt-3 ligand, IL-5) were significantly decreased; IFN-γ plasma levels were unchanged. PFTs showed minimal change in FVC. Post hoc analysis indicated that the slope of decline in TLC and DLCO reversed after beginning therapy. The 6-min walk was unchanged.

Conclusions: IFN-γ is safe in IPF and can be effectively delivered to lung parenchyma. PFTs remained stable throughout the trial. Reversal of pretherapy PFT decline may define an end-point for future clinical trials.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Inhalation
  • Aerosols
  • Aged
  • Antiviral Agents / administration & dosage
  • Antiviral Agents / adverse effects
  • Antiviral Agents / therapeutic use*
  • Bronchoalveolar Lavage
  • Cytokines / metabolism
  • Female
  • Humans
  • Idiopathic Pulmonary Fibrosis / drug therapy*
  • Idiopathic Pulmonary Fibrosis / physiopathology
  • Interferon-gamma / administration & dosage
  • Interferon-gamma / adverse effects
  • Interferon-gamma / therapeutic use*
  • Male
  • Middle Aged
  • Pulmonary Diffusing Capacity
  • Retrospective Studies
  • Total Lung Capacity
  • Vital Capacity


  • Aerosols
  • Antiviral Agents
  • Cytokines
  • Interferon-gamma