title: Aerosolized interferon-alpha treatment in patients with multi-drug-resistant pulmonary tuberculosis.
abstract: Multi-drug-resistant tuberculosis (MDR-TB) has emerged as an obstacle to the control of tuberculosis. Recent data however, suggest that interferon-(IFN)-gamma and IFN-alpha may improve disease evolution in subjects affected with pulmonary tuberculosis caused by multi-resistant (IFN-gamma) and sensitive (IFN-alpha) strains. The mechanisms involved are not known, even though it has been reported that IFN-gamma-secreting CD4+ Th cells may possess antitubercular effects. In addition, IFN-alpha can induce IFN-gamma secretion by CD4+ Th cells, and both types of IFN may stimulate macrophage activities. The aim of this study was to explore the possibility that aerosolized IFN-alpha, administered concomitantly with conventional antitubercular chemotherapy, may improve the course of pulmonary tuberculosis. After six months of directly observed therapy (DOT), seven patients who were non-responders to a second line antitubercular therapy were given an IFN-alpha aerosol (3 MU, three times a week) for two months as adjunctive therapy. All strains were resistant to at least two first-line drugs. After IFN-alpha administration, the patients were followed up for a further six months with the same DOT. Sputum samples were collected monthly during the study period, with the exception of the IFN-alpha administration period, when the observations were performed weekly. High resolution computed tomography (HRCT) chest scans were performed before and after IFN-alpha inhalations. The analysis of the results showed that the mean number of Mycobacterium tuberculosis (Mt) had remained statistically unchanged (p = 0.80) during the first 6 months of DOT. During the following 2 months of IFN-alpha administration, 5 patients became negative (p = 0.02). After the end of treatment a progressive increase in Mt number was observed (p = 0. 02). Sputum cultures remained positive for all patients throughout the study period, although a significant decrease (p = 0.02) in the colony number per culture was observed after adjunctive treatment with IFN-alpha. After stopping administration of IFN-alpha, a significant increase (p = 0.03) in the colony number per culture was noted as well as in Mt numbers. HRCT scans were slightly improved in all patients. These preliminary data suggest that aerosolized IFN-alpha may be a promising adjunctive therapy for patients with MDR-TB. Optimal doses and schedules however, require further studies.
authors.affiliation: Istituto Lazzaro Spallanzani, IRCCS, Clinica Malattie dell'Apparato Respiratorio, Via Portuense 292, 00149 Roma (Italia). giosue.s@flashnet.it
authors.forename: S
authors.initials: S
authors.lastname: Giosuè
authors.forename: M
authors.initials: M
authors.lastname: Casarini
authors.forename: F
authors.initials: F
authors.lastname: Ameglio
authors.forename: P
authors.initials: P
authors.lastname: Zangrilli
authors.forename: M
authors.initials: M
authors.lastname: Palla
authors.forename: A M
authors.initials: AM
authors.lastname: Altieri
authors.forename: A
authors.initials: A
authors.lastname: Bisetti
mesh_terms: D000328:Adult; D000336:Aerosols; D000995:Antitubercular Agents / Q000494:pharmacology / Q000627:therapeutic use; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D018432:Drug Resistance, Multiple; D005260:Female; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage / Q000627:therapeutic use*; D007378:Interleukins / Q000032:analysis; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000302:isolation & purification; D013183:Sputum / Q000382:microbiology; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
chemical_list: D000336:Aerosols; D000995:Antitubercular Agents; D016898:Interferon-alpha; D007378:Interleukins; D014409:Tumor Necrosis Factor-alpha