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

Depts of ¹ Medicine and ² Paediatrics, University of Washington, Seattle, WA, USA

CORRESPONDENCE: T.S. Hallstrand, Division of Pulmonary and Critical Care, Dept of Medicine, University of Washington, Box 356522, 1959 NE Pacific Street, Seattle, WA, 98195, USA. Fax: 1 2066858673. E-mail: tealh@u.washington.edu

Keywords: Bronchiectasis, host defences, interferon-, mycobacterium, treatment, tumour necrosis factor-

Received: March 29, 2004
Accepted April 27, 2004

This study was supported by the National Institutes of Health grants HL04231 (T.S. Hallstrand) and HL62995 (W.C. Liles).

Pulmonary infection with nontuberculous mycobacteria (NTM) in previously healthy human immunodeficiency virus-seronegative individuals is difficult to treat. Recently, functional interferon (IFN)- deficiency has been identified in individuals susceptible to this disease. Treatment with inhaled IFN- for NTM pulmonary disease associated with functional IFN- deficiency has not been previously described.

In this study, the IFN- pathway was characterised in an individual who had progressive NTM pulmonary infection, despite appropriate multidrug antibiotic therapy, and 10 healthy controls. Levels of IFN- and tumour necrosis factor- 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-1b (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- with and without physiological stimuli was consistent with functional IFN- deficiency in the affected individual. There was no evidence of mutation in the coding regions of IL-12p35, IL-12p40, IL-12Rß1 and IL-18 in the affected individual. Treatment with inhaled IFN- resulted in rapid and sustained clearance of the organism from the airways and stabilisation of lung function.

In conclusion, inhaled interferon- can be effective for the treatment of nontuberculous mycobacteria pulmonary disease associated with functional interferon- deficiency.

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