Immunomodulation with recombinant interferon-gamma1b in pulmonary tuberculosis.

<h4>Background</h4>Current treatment regimens for pulmonary tuberculosis require at least 6 months of therapy. Immune adjuvant therapy with recombinant interferon-gamma1b (rIFN-gammab) may reduce pulmonary inflammation and reduce the period of infectivity by promoting earlier sputum clea...

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Main Authors: Rod Dawson, Rany Condos, Doris Tse, Maryann L Huie, Stanley Ress, Chi-Hong Tseng, Clint Brauns, Michael Weiden, Yoshihiko Hoshino, Eric Bateman, William N Rom
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2009-09-01
Series:PLoS ONE
Online Access:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0006984&type=printable
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Summary:<h4>Background</h4>Current treatment regimens for pulmonary tuberculosis require at least 6 months of therapy. Immune adjuvant therapy with recombinant interferon-gamma1b (rIFN-gammab) may reduce pulmonary inflammation and reduce the period of infectivity by promoting earlier sputum clearance.<h4>Methodology/principal findings</h4>We performed a randomized, controlled clinical trial of directly observed therapy (DOTS) versus DOTS supplemented with nebulized or subcutaneously administered rIFN-gamma1b over 4 months to 89 patients with cavitary pulmonary tuberculosis. Bronchoalveolar lavage (BAL) and blood were sampled at 0 and 4 months. There was a significant decline in levels of inflammatory cytokines IL-1beta, IL-6, IL-8, and IL-10 in 24-hour BAL supernatants only in the nebulized rIFN-gamma1b group from baseline to week 16. Both rIFN-gamma1b groups showed significant 3-fold increases in CD4+ lymphocyte response to PPD at 4 weeks. There was a significant (p = 0.03) difference in the rate of clearance of Mtb from the sputum smear at 4 weeks for the nebulized rIFN-gamma1b adjuvant group compared to DOTS or DOTS with subcutaneous rIFN-gamma1b. In addition, there was significant reduction in the prevalence of fever, wheeze, and night sweats at 4 weeks among patients receiving rFN-gamma1b versus DOTS alone.<h4>Conclusion</h4>Recombinant interferon-gamma1b adjuvant therapy plus DOTS in cavitary pulmonary tuberculosis can reduce inflammatory cytokines at the site of disease, improve clearance of Mtb from the sputum, and improve constitutional symptoms.<h4>Trial registration</h4>ClinicalTrials.gov NCT00201123.
ISSN:1932-6203