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.
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.
Lee
J-S
JS
Department of Microbiology, College of Medicine, Chungnam National University, Daejeon, Korea.
Song
C-H
CH
Lim
J-H
JH
Kim
H-J
HJ
Park
J-K
JK
Paik
T-H
TH
Kim
C-H
CH
Kong
S-J
SJ
Shon
M-H
MH
Jung
S-S
SS
Jo
E-K
EK
D000942:Antigens, Bacterial / Q000276:immunology*; D002478:Cells, Cultured; D006801:Humans; D007108:Immune Tolerance; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D016209:Interleukin-8 / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D009169:Mycobacterium tuberculosis / Q000276:immunology; D017211:Treatment Failure; D014373:Tuberculin / Q000276:immunology; D018088:Tuberculosis, Multidrug-Resistant / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000276:immunology
D000942:Antigens, Bacterial; D016209:Interleukin-8; D014373:Tuberculin; D014409:Tumor Necrosis Factor-alpha; C072681:Mycobacterium tuberculosis antigens; D007371:Interferon-gamma