Inhaled IFN-gamma for persistent nontuberculous mycobacterial pulmonary disease due to functional IFN-gamma...

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.