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Decreased phosphorylation of STAT-1, STAT-4 and cytokine release in MDR-TB patients with primary resistance

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Authors
Kim, H. J.; Chung, D. H.; Kim, M. J,; Jang, J. H.; Kim, Y. W.; Han, S. K.; Shim, Y-W.; Yim, J-J.
Issue Date
2008
Publisher
International Union Against Tuberculosis and Lung Disease
Citation
Int J Tuberc Lung Dis 2008; 12: 1071-1076
Keywords
MDR-TB; IFN-γ; IL-12; TNF-α; pSTAT-4; pSTAT-1
Abstract
SETTING: We recently showed that treatment failure rate was higher among multidrug-resistant tuberculosis (MDR-TB) patients without a previous history of tuberculosis (TB) treatment, or so-called `primary resistance'.

OBJECTIVE: To investigate the phosphorylation levels of signal transducers and activators of transcription-1 (STAT-1) and STAT-4 and the subsequent cytokine release as a possible cause of a poor prognosis in MDR-TB patients with primary resistance.

DESIGN: Ten patients with successfully treated pulmonary TB without resistance, 12 MDR-TB patients with acquired resistance and 10 MDR-TB patients with primary resistance were enrolled. After 24 h stimulation of peripheral blood mononuclear cells (PBMC) with interferon-gamma (IFN-γ), interleukin-12 (IL-12), purified protein derivative (PPD), or lysate of Mycobacterium tuberculosis, flow cytometric analysis of intracellular pSTAT-1 and pSTAT-4 were performed and secretion of IFN-γ, IL-12p40 and tumour necrosis factor-alpha (TNF-α) was measured in culture supernatant.

RESULTS: The mean fluorescent intensities of pSTAT-1 and pSTAT-4 in PBMC of MDR-TB patients with primary resistance decreased on stimulation of IFN-γ, PPD or lysate of M. tuberculosis when compared with patients with acquired resistance. In addition, secretion of IFN-γ, IL-12p40 and TNF-α in these patients decreased on various stimuli.

CONCLUSION: Decreased phosphorylation of STAT-1, STAT-4, and of subsequent cytokine release, might be associated with a poor prognosis in MDR-TB patients with primary resistance.
ISSN
1027-3719 (print)1815-7920 (online)
Language
English
URI
http://www.ingentaconnect.com/content/iuatld/ijtld/2008/00000012/00000009/art00016
http://hdl.handle.net/10371/4615
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College of Medicine/School of Medicine (의과대학/대학원)Pathology (병리학전공)Journal Papers (저널논문_병리학전공)
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