RT Journal Article
SR Electronic
T1 Inhaled IFN-γ for persistent nontuberculous mycobacterial pulmonary disease due to functional IFN-γ deficiency
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP 367
OP 370
DO 10.1183/09031936.04.00036704
VO 24
IS 3
A1 T.S. Hallstrand
A1 H.D. Ochs
A1 Q. Zhu
A1 W.C. Liles
YR 2004
UL http://erj.ersjournals.com/content/24/3/367.abstract
AB Pulmonary infection with nontuberculous mycobacteria (NTM) in previously healthy human immunodeficiency virus-seronegative individuals is difficult to treat. Recently, functional interferon (IFN)-γ deficiency has been identified in individuals susceptible to this disease. Treatment with inhaled IFN-γ for NTM pulmonary disease associated with functional IFN-γ deficiency has not been previously described. In this study, the IFN-γ pathway was characterised in an individual who had progressive NTM pulmonary infection, despite appropriate multidrug antibiotic therapy, and 10 healthy controls. Levels of IFN-γ and tumour necrosis factor-α in whole blood were assessed before and after incubation with lipopolysaccharide, heat-killed Escherichia coli, heat-killed Staphylococcus aureus and phorbol myristate acetate/ionomycin. The coding regions of interleukin (IL)-12, IL-18 and the IL-12 receptor were sequenced using nested primers. IFN-γ1b (100 µg·dose−1) was administered to the affected individual by ultrasonic nebuliser 3 days·week−1 for 3 months. In vitro whole blood production of IFN-γ with and without physiological stimuli was consistent with functional IFN-γ deficiency in the affected individual. There was no evidence of mutation in the coding regions of IL-12p35, IL-12p40, IL-12Rβ1 and IL-18 in the affected individual. Treatment with inhaled IFN-γ resulted in rapid and sustained clearance of the organism from the airways and stabilisation of lung function. In conclusion, inhaled interferon-γ can be effective for the treatment of nontuberculous mycobacteria pulmonary disease associated with functional interferon-γ deficiency. This study was supported by the National Institutes of Health grants HL04231 (T.S. Hallstrand) and HL62995 (W.C. Liles).