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The production of tumour necrosis factor-alpha is decreased in peripheral blood mononuclear cells from multidrug-resistant tuberculosis patients following stimulation with the 30-kDa antigen of Mycobacterium tuberculosis.

Abstract
The clearance of intracellular bacteria requires the appropriate induction of proinflammatory cytokines and chemokines to recruit macrophages and T cells to the site of infection. In this study, we investigated the production of tumour necrosis factor (TNF)-alpha, interleukin (IL)-8 and interferon (IFN)-gamma by the peripheral blood mononuclear cells (PBMC) of patients with multidrug-resistant tuberculosis (MDR-TB) in response to in vitro stimulation with the 30-kDa antigen of Mycobacterium tuberculosis. The results were compared with those from cases of newly diagnosed TB (N-TB) and TB with treatment failure (TF-TB), and healthy tuberculin reactors (HTR). The most significantly depressed TNF-alpha levels were found in MDR-TB patients. IFN-gamma production was depressed significantly in all groups of TB patients compared with the HTR group. TNF-alpha secretion in response to the 30-kDa antigen was unchanged by coculturing with recombinant human interferon (rhIFN)-gamma, and was increased dramatically following IL-10 neutralization with an anti-human IL-10 antibody. The IL-8 levels were depressed significantly in MDR-TB patients compared with N-TB patients, but were similar to the IL-8 levels in TF-TB patients. Furthermore, rhTNF-alpha directly increased IL-8 secretion, and neutralizing antibody to TNF-alpha inhibited IL-8 production by the PBMC of MDR-TB patients that were stimulated with the 30-kDa antigen. Taken together, these data suggest that the PBMC of MDR-TB patients typically show TNF-alpha depression in response to the 30-kDa antigen, and this effect is modulated by IL-10. In addition, we highlight the role of TNF-alpha in IL-8 secretion in MDR-TB patients.
AuthorsJ-S Lee, C-H Song, J-H Lim, H-J Kim, J-K Park, T-H Paik, C-H Kim, S-J Kong, M-H Shon, S-S Jung, E-K Jo
JournalClinical and experimental immunology (Clin Exp Immunol) Vol. 132 Issue 3 Pg. 443-9 (Jun 2003) ISSN: 0009-9104 [Print] England
PMID12780691 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antigens, Bacterial
  • Interleukin-8
  • Tuberculin
  • Tumor Necrosis Factor-alpha
  • Mycobacterium tuberculosis antigens
  • Interferon-gamma
Topics
  • Antigens, Bacterial (immunology)
  • Cells, Cultured
  • Humans
  • Immune Tolerance
  • Interferon-gamma (biosynthesis, immunology)
  • Interleukin-8 (biosynthesis)
  • Leukocytes, Mononuclear (immunology)
  • Lymphocyte Activation (immunology)
  • Mycobacterium tuberculosis (immunology)
  • Treatment Failure
  • Tuberculin (immunology)
  • Tuberculosis, Multidrug-Resistant (immunology)
  • Tumor Necrosis Factor-alpha (biosynthesis, immunology)

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