Depression of Both Interferon-gamma and Tumor Necrosis Factor-alpha Production by Peripheral Blood Mononuclear Cells from Chronic Refractory Tuberculosis Patients

ABSTRACT

Understanding human immune responses in chronic refractory tuberculosis (CRTB) is important for developing immunotherapy against the disease. The aim of this study was to examine cytokine responses [interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and IL-10] by peripheral blood mononuclear cells (PBMCs) in CRTB patients after in vitro stimulation with the 30-kDa or purified protein derivative (PPD) antigen (Ag). Most of the CRTB cases were multidrug-resistant (MDR) TB. The results were compared with those from early TB (E-TB) patients and healthy tuberculin reactors (HTR). IFN-gamma production was significantly depressed in both CRTB and E-TB groups compared with HTR. In response to the 30-kDa Ag, TNF-alpha levels were significantly depressed only in CRTB patients, while greatly increased in E-TB patients. In addition, IL-10 production was significantly increased in E-TB patients, and PBMC from both E-TB and CRTB patients secreted more IL-6 than HTR. IL-10 neutralization significantly increased TNF-alpha levels, whereas anti-TNF-alpha did not alter IL-10 induction significantly in PBMC from HTR and CRTB patients. Our findings suggest that CRTB patients have depression in both IFN-gamma and TNF-alpha reponses, which might play important roles during chronic M. tuberculosis infection.