Depressed interleukin-12 production by peripheral blood mononuclear cells after in vitro stimulation with the 30-kDa antigen in recurrent pulmonary tuberculosis patients.
Some patients develop recurrent tuberculosis (R-TB), even after successfully completing initial anti-tubercular treatment. Although R-TB may be caused by relapse or exogenous reinfection, little is known about the underlying host responses associated with R-TB. This study investigated the profile of cytokines [interferon (IFN)-gamma, interleukin (IL)-12, tumor necrosis factor (TNF)-alpha, IL-6, and IL-10] present in peripheral blood mononuclear cells (PBMCs) of 17 R-TB patients after stimulation with the 30-kDa antigen (Ag) or purified protein derivative (PPD) Ag of Mycobacterium tuberculosis. These data were compared with data obtained from 15 patients with newly diagnosed pulmonary TB (N-TB), 22 patients with treatment failure (TF-TB), and 19 healthy tuberculin reactors (HTR). N-TB and R-TB patients were enrolled in this study within 1 month of beginning anti-tubercular chemotherapy. ELISA results showed that IFN-gamma production following stimulation with the 30-kDa Ag was significantly lower in each group of TB patients than in the HTR controls. In addition, patients with R-TB showed the most significant IL-12 depression among the subject groups after in vitro stimulation with either Ag. Furthermore, a significant decrease in TNF-alpha and IL-10 levels was observed in R-TB patients relative to N-TB patients. However, there was no statistical difference in TNF-alpha and IL-10 production between R-TB patients, TF-TB patients, and HTR controls. Our findings suggest that the underlying mechanisms of cytokine regulation might differ between N-TB and R-TB patients, and that decreased IL-12 production in response to the 30-kDa or PPD Ag might be involved in the immunopathogenesis of human R-TB.
Department of Microbiology, College of Medicine, Chungnam National University, 6 Munhwa-dong, Jung-ku, Taejon 301-747, Republic of Korea.
Ji-Sook
JS
Lee
Chang-Hwa
CH
Song
Chul-Hee
CH
Kim
Suck-Jun
SJ
Kong
Mal-Hyun
MH
Shon
Ji-Won
JW
Suhr
Sung-Soo
SS
Jung
Jae-Hyun
JH
Lim
Hwa-Jung
HJ
Kim
Jeong-Kyu
JK
Park
Tae-Hyun
TH
Paik
Eun-Kyeong
EK
Jo
D000942:Antigens, Bacterial / Q000276:immunology*; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis*; D007378:Interleukins / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008213:Lymphocyte Activation; D009169:Mycobacterium tuberculosis / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014397:Tuberculosis, Pulmonary / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D000942:Antigens, Bacterial; D007378:Interleukins; D014409:Tumor Necrosis Factor-alpha; C072681:Mycobacterium tuberculosis antigens; D018664:Interleukin-12; D007371:Interferon-gamma