Immunomodulation with recombinant interferon-γ1b in pulmonary tuberculosis

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dc.contributor.authorDawson, Roden_ZA
dc.contributor.authorCondos, Ranyen_ZA
dc.contributor.authorTse, Dorisen_ZA
dc.contributor.authorHuie, Maryann Len_ZA
dc.contributor.authorRess, Stanleyen_ZA
dc.contributor.authorTseng, Chi-Hongen_ZA
dc.contributor.authorBrauns, Clinten_ZA
dc.contributor.authorWeiden, Michaelen_ZA
dc.contributor.authorHoshino, Yoshihikoen_ZA
dc.contributor.authorBateman, Ericen_ZA
dc.date.accessioned2015-12-28T06:45:28Z
dc.date.available2015-12-28T06:45:28Z
dc.date.issued2009en_ZA
dc.description.abstractBACKGROUND: Current treatment regimens for pulmonary tuberculosis require at least 6 months of therapy. Immune adjuvant therapy with recombinant interferon-γ1b (rIFN-γb) may reduce pulmonary inflammation and reduce the period of infectivity by promoting earlier sputum clearance. METHODOLOGY/PRINCIPAL FINDINGS: We performed a randomized, controlled clinical trial of directly observed therapy (DOTS) versus DOTS supplemented with nebulized or subcutaneously administered rIFN-γ1b 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-1β, IL-6, IL-8, and IL-10 in 24-hour BAL supernatants only in the nebulized rIFN-γ1b group from baseline to week 16. Both rIFN-γ1b 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-γ1b adjuvant group compared to DOTS or DOTS with subcutaneous rIFN-γ1b. In addition, there was significant reduction in the prevalence of fever, wheeze, and night sweats at 4 weeks among patients receiving rFN-γ1b versus DOTS alone. CONCLUSION: Recombinant interferon-γ1b 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. Trial Registration ClinicalTrials.gov NCT00201123en_ZA
dc.identifier.apacitationDawson, R., Condos, R., Tse, D., Huie, M. L., Ress, S., Tseng, C., ... Bateman, E. (2009). Immunomodulation with recombinant interferon-γ1b in pulmonary tuberculosis. <i>PLoS One</i>, http://hdl.handle.net/11427/16017en_ZA
dc.identifier.chicagocitationDawson, Rod, Rany Condos, Doris Tse, Maryann L Huie, Stanley Ress, Chi-Hong Tseng, Clint Brauns, Michael Weiden, Yoshihiko Hoshino, and Eric Bateman "Immunomodulation with recombinant interferon-γ1b in pulmonary tuberculosis." <i>PLoS One</i> (2009) http://hdl.handle.net/11427/16017en_ZA
dc.identifier.citationDawson, R., Condos, R., Tse, D., Huie, M. L., Ress, S., Tseng, C. H., ... & Rom, W. N. (2009). Immunomodulation with recombinant interferon-γ1b in pulmonary tuberculosis. PLoS ONE, 4(9). doi:10.1371/journal.pone.0006984en_ZA
dc.identifier.ris TY - Journal Article AU - Dawson, Rod AU - Condos, Rany AU - Tse, Doris AU - Huie, Maryann L AU - Ress, Stanley AU - Tseng, Chi-Hong AU - Brauns, Clint AU - Weiden, Michael AU - Hoshino, Yoshihiko AU - Bateman, Eric AB - BACKGROUND: Current treatment regimens for pulmonary tuberculosis require at least 6 months of therapy. Immune adjuvant therapy with recombinant interferon-γ1b (rIFN-γb) may reduce pulmonary inflammation and reduce the period of infectivity by promoting earlier sputum clearance. METHODOLOGY/PRINCIPAL FINDINGS: We performed a randomized, controlled clinical trial of directly observed therapy (DOTS) versus DOTS supplemented with nebulized or subcutaneously administered rIFN-γ1b 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-1β, IL-6, IL-8, and IL-10 in 24-hour BAL supernatants only in the nebulized rIFN-γ1b group from baseline to week 16. Both rIFN-γ1b 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-γ1b adjuvant group compared to DOTS or DOTS with subcutaneous rIFN-γ1b. In addition, there was significant reduction in the prevalence of fever, wheeze, and night sweats at 4 weeks among patients receiving rFN-γ1b versus DOTS alone. CONCLUSION: Recombinant interferon-γ1b 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. Trial Registration ClinicalTrials.gov NCT00201123 DA - 2009 DB - OpenUCT DO - 10.1371/journal.pone.0006984 DP - University of Cape Town J1 - PLoS One LK - https://open.uct.ac.za PB - University of Cape Town PY - 2009 T1 - Immunomodulation with recombinant interferon-γ1b in pulmonary tuberculosis TI - Immunomodulation with recombinant interferon-γ1b in pulmonary tuberculosis UR - http://hdl.handle.net/11427/16017 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/16017
dc.identifier.urihttp://dx.doi.org/10.1371/journal.pone.0006984
dc.identifier.vancouvercitationDawson R, Condos R, Tse D, Huie ML, Ress S, Tseng C, et al. Immunomodulation with recombinant interferon-γ1b in pulmonary tuberculosis. PLoS One. 2009; http://hdl.handle.net/11427/16017.en_ZA
dc.language.isoengen_ZA
dc.publisherPublic Library of Scienceen_ZA
dc.publisher.departmentDivision of Pulmonologyen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.rightsThis is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en_ZA
dc.rights.holder© 2009 Dawson et alen_ZA
dc.rights.urihttp://creativecommons.org/licenses/by/4.0en_ZA
dc.sourcePLoS Oneen_ZA
dc.source.urihttp://journals.plos.org/plosoneen_ZA
dc.subject.otherMycobacterium tuberculosisen_ZA
dc.subject.otherTuberculosisen_ZA
dc.subject.otherSputumen_ZA
dc.subject.otherCytokinesen_ZA
dc.subject.otherInflammationen_ZA
dc.subject.otherLymphocytesen_ZA
dc.subject.otherFeversen_ZA
dc.subject.otherNeutrophilsen_ZA
dc.titleImmunomodulation with recombinant interferon-γ1b in pulmonary tuberculosisen_ZA
dc.typeJournal Articleen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceArticleen_ZA
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