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

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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.

Keywords: IFN-γ; IL-12; MDR-TB; TNF-α; pSTAT-1; pSTAT-4

Document Type: Regular Paper

Affiliations: 1: Department of Pathology and Clinical Research Center, Seoul National University College of Medicine, Seoul, Republic of Korea 2: Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine and Lung Institute, Seoul National University College of Medicine, Seoul, Republic of Korea 3: Department of Internal Medicine, Ewha Womans University College of Medicine, Seoul, Republic of Korea

Publication date: September 1, 2008

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  • The International Journal of Tuberculosis and Lung Disease publishes articles on all aspects of lung health, including public health-related issues such as training programmes, cost-benefit analysis, legislation, epidemiology, intervention studies and health systems research. The IJTLD is dedicated to the continuing education of physicians and health personnel and the dissemination of information on tuberculosis and lung health world-wide.

    Certain IJTLD articles are selected for translation into French, Spanish, Chinese or Russian. They are available on the Union website

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