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Home / The International Journal of Tuberculosis and Lung Disease, Volume 12, Number 9

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

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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: 01 September 2008

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  • The International Journal of Tuberculosis and Lung Disease (IJTLD) is for clinical research and epidemiological studies on lung health, including articles on TB, TB-HIV and respiratory diseases such as COVID-19, asthma, COPD, child lung health and the hazards of tobacco and air pollution. Individuals and institutes can subscribe to the IJTLD online or in print – simply email us at [email protected] for details.

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