Subcutaneously administered interferon-gamma for the treatment of multidrug-resistant pulmonary tuberculosis

Objective: We evaluated the clinical and laboratory effects of subcutaneously administered interferon-gamma (IFN-gamma) in the treatment of chronic and advanced multidrug-resistant tuberculosis (MDR-TB). Design: Eight patients with sputum smear and culture persistently positive MDR-TB were subcutaneously administered 2 million international units of recombinant human IFN-gamma three times a week for 24 weeks (72 doses total) between December 2002 and May 2003. Subjects also received a customized drug regimen containing second- and third-time antituberculosis agents based upon drug susceptibility testing and previous treatment history. Results: Body weight remained stable or slightly decreased in all subjects during the study period, and none displayed radiographic improvement on serial chest computed tomography scanning. Sputum smears and cultures remained positive for all patients, and there was no increase in the mean time to yield a positive culture (from 16.5 +/- 6.4 to 11.8 +/- 4.9 days). There was no enhancement of cell-mediated immune responses in terms of production of IFN-gamma or IL-10, or of composition of lymphocytes among peripheral blood mononuclear cells. In four patients, therapy was discontinued because of adverse reactions. Conclusion: In patients with chronic and advanced MDR-TB, subcutaneous IFN-gamma treatment did not result in improvement in clinical, radiologic, microbiologic, or immunologic parameters. (C) 2007 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.