Regional deposition of aerosolized interferon-γ in pulmonary tuberculosis

Study objectives: Aerosol interferon-γ (IFN-γ) is a potential immunomodulator in the treatment of pulmonary tuberculosis (TB). Previous investigations demonstrated conversion of sputum smears in five patients with multidrug-resistant TB after 12 treatments over 1 month, and induction of signaling molecules in 10 of 11 drug-sensitive TB patients using BAL. The objective of the current study was to evaluate particle size and deposition pattern in patients with TB receiving aerosol IFN-γ treatment. Design: Particle size was determined with a cascade impactor, and deposition of IFN-γ mixed with ^99mTc-labeled human serum albumin was assessed using a gamma camera. Local levels of IFN-γ were measured in BAL using enzyme-linked immunosorbent assays. Study patients/intervention: Fourteen patients with pulmonary TB received IFN-γ aerosol (500 μg) for 12 treatments in addition to antimycobacterial therapy with BAL before and after IFN-γ aerosol treatment. Eight patients with minimal-to-moderate parenchymal involvement underwent deposition studies. Deposited ^99mTc-labeled IFN-γ aerosol was partitioned between upper airways and lungs using attenuation correction measurements. ¹³³Xe equilibrium scanning, ¹³³Xe washout, and ^99mTc- macroaggregate injection defined regional lung volume, ventilation, and perfusion. Results: Upper airway deposition was significant often exceeding lung deposition (53.9 ± 7.09 μg vs 35.8 ± 2.73 μg, respectively [mean ± SE]). IFN-γ levels measured in BAL fluid were significantly increased with aerosol treatment (0.83 ± 0.43 μg before vs 24.76 ± 8.71 μg after, p ≤ 0.017), and IFN-γ levels correlated with regional deposition of IFN-γ aerosol (r = 0.823). Four-quadrant analysis of regional lung deposition best correlated with regional perfusion (r = 0.422, p = 0.013) with penetration of aerosol into areas of obvious radiographic infiltration on chest radiograph. Conclusions: Aerosol therapy with IFN-γ in patients with pulmonary TB is widely distributed and results in significant enhancement of IFN-γ levels in the lower respiratory tract. In patients without lung destruction, IFN-γ aerosol may be an adjuvant to enhance the local immune response.