Document Detail


Decreased phosphorylation of STAT-1, STAT-4 and cytokine release in MDR-TB patients with primary resistance.
MedLine Citation:
PMID:  18713507     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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-gamma), 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-gamma, IL-12p40 and tumour necrosis factor-alpha (TNF-alpha) 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-gamma, PPD or lysate of M. tuberculosis when compared with patients with acquired resistance. In addition, secretion of IFN-gamma, IL-12p40 and TNF-alpha 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.
Authors:
H J Kim; D H Chung; M J Kim; J H Jang; Y W Kim; S K Han; Y-S Shim; J-J Yim
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease     Volume:  12     ISSN:  1027-3719     ISO Abbreviation:  Int. J. Tuberc. Lung Dis.     Publication Date:  2008 Sep 
Date Detail:
Created Date:  2008-08-20     Completed Date:  2008-12-16     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9706389     Medline TA:  Int J Tuberc Lung Dis     Country:  France    
Other Details:
Languages:  eng     Pagination:  1071-6     Citation Subset:  IM    
Affiliation:
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine and Lung Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
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MeSH Terms
Descriptor/Qualifier:
Adolescent
Adult
Cytokines / metabolism*
Enzyme-Linked Immunosorbent Assay
Female
Flow Cytometry
Humans
Leukocytes, Mononuclear / chemistry,  immunology
Male
Middle Aged
Mycobacterium tuberculosis / immunology*
Phosphorylation
STAT1 Transcription Factor / metabolism*
STAT4 Transcription Factor / metabolism*
Tuberculosis, Multidrug-Resistant / blood,  drug therapy,  immunology,  metabolism*
Tuberculosis, Pulmonary / drug therapy,  immunology*,  metabolism,  microbiology
Chemical
Reg. No./Substance:
0/Cytokines; 0/STAT1 Transcription Factor; 0/STAT1 protein, human; 0/STAT4 Transcription Factor; 0/STAT4 protein, human

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