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

• Published in: Clinical and experimental immunology 2003-06, Vol.132 (3), p.443-449
• Main Authors: LEE, J.‐S., SONG, C.‐H., LIM, J.‐H., KIM, H.‐J., PARK, J.‐K., PAIK, T.‐H., KIM, C.‐H., KONG, S.‐J., SHON, M.‐H., JUNG, S.‐S., JO, E.‐K.
• Format: Article
• Language: English
• Subjects: 30‐kDa antigen; Antibacterial agents; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antigens, Bacterial - immunology; Bacterial diseases; Biological and medical sciences; Cells, Cultured; Clinical Studies; Human bacterial diseases; Humans; Immune Tolerance; Infectious diseases; Interferon-gamma - biosynthesis; Interferon-gamma - immunology; interferon‐gamma; Interleukin-8 - biosynthesis; interleukin‐8; Leukocytes, Mononuclear - immunology; Lymphocyte Activation - immunology; Medical sciences; multidrug‐resistant tuberculosis; Mycobacterium tuberculosis - immunology; Pharmacology. Drug treatments; Treatment Failure; Tuberculin - immunology; Tuberculosis and atypical mycobacterial infections; Tuberculosis, Multidrug-Resistant - immunology; Tumor Necrosis Factor-alpha - biosynthesis; Tumor Necrosis Factor-alpha - immunology; tumour necosis factor‐alpha
• ISSN: 0009-9104; 1365-2249
• DOI: 10.1046/j.1365-2249.2003.02172.x

SUMMARY 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)‐α, interleukin (IL)‐8 and interferon (IFN)‐γ 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‐α levels were found in MDR‐TB patients. IFN‐γ production was depressed significantly in all groups of TB patients compared with the HTR group. TNF‐α secretion in response to the 30‐kDa antigen was unchanged by coculturing with recombinant human interferon (rhIFN)‐γ, 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‐α directly increased IL‐8 secretion, and neutralizing antibody to TNF‐α 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‐α depression in response to the 30‐kDa antigen, and this effect is modulated by IL‐10. In addition, we highlight the role of TNF‐α in IL‐8 secretion in MDR‐TB patients.