title: Inhaled IFN-gamma for persistent nontuberculous mycobacterial pulmonary disease due to functional IFN-gamma deficiency.
abstract: Pulmonary infection with nontuberculous mycobacteria (NTM) in previously healthy human immunodeficiency virus-seronegative individuals is difficult to treat. Recently, functional interferon (IFN)-gamma deficiency has been identified in individuals susceptible to this disease. Treatment with inhaled IFN-gamma for NTM pulmonary disease associated with functional IFN-gamma deficiency has not been previously described. In this study, the IFN-gamma pathway was characterised in an individual who had progressive NTM pulmonary infection, despite appropriate multidrug antibiotic therapy, and 10 healthy controls. Levels of IFN-gamma and tumour necrosis factor-alpha 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-gamma1b (100 microg.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-gamma with and without physiological stimuli was consistent with functional IFN-gamma deficiency in the affected individual. There was no evidence of mutation in the coding regions of IL-12p35, IL-12p40, IL-12Rbeta1 and IL-18 in the affected individual. Treatment with inhaled IFN-gamma resulted in rapid and sustained clearance of the organism from the airways and stabilisation of lung function. In conclusion, inhaled interferon-gamma can be effective for the treatment of nontuberculous mycobacteria pulmonary disease associated with functional interferon-gamma deficiency.
authors.affiliation: Division of Pulmonary and Critical Care, Dept of Medicine, University of Washington, Box 356522, 1959 NE Pacific Street, Seattle, WA, 98195, USA. tealh@u.washington.edu
authors.forename: T S
authors.initials: TS
authors.lastname: Hallstrand
authors.forename: H D
authors.initials: HD
authors.lastname: Ochs
authors.forename: Q
authors.initials: Q
authors.lastname: Zhu
authors.forename: W C
authors.initials: WC
authors.lastname: Liles
mesh_terms: D000280:Administration, Inhalation; D000328:Adult; D001987:Bronchiectasis / Q000188:drug therapy / Q000209:etiology; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000008:administration & dosage / Q000172:deficiency* / Q000627:therapeutic use*; D008171:Lung Diseases / Q000188:drug therapy* / Q000276:immunology / Q000382:microbiology; D008297:Male; D008875:Middle Aged; D009164:Mycobacterium Infections / Q000188:drug therapy* / Q000276:immunology; D015270:Mycobacterium avium-intracellulare Infection / Q000188:drug therapy* / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma