Dysregulated Production of IFN-g, IL-12, and IL-10 by Peripheral Blood Mononuclear Cells from Early Active Pulmonary and Multidrug-Resistant Tuberculosis Patients

ABSTRACT

In this study, we investigated profiles of the cytokines IFN-g, IL-12, and IL-10 in active pulmonary tuberculosis (EAPTB) patients, HIV-negative patients with multidrug-resistant tuberculosis (MDR-TB) and in healthy tuberculin reactors (HTR). We studied the responses of peripheral blood mononuclear cells (PBMC) from 12 EAPTB patients and 15 MDR-TB patients to stimulation with a purified protein derivatives (PPD) antigen (Ag), and compared them with those from 14 HTR. Using ELISA, IFN-g production was found to be significantly depressed, while IL-10 was significantly elevated in both MDR-TB and EAPTB after in vitro stimulation with PPD, compared with those in HTR. Although there was no significant difference in IL-12 production among the three groups, mean IL-12 production was highest in patients with MDR-TB. In these patients, IL-12 production was significantly correlated with IL-10 expression, but not IFN-g production. In addition, neutralization of endogenous IL-10 led to enhanced IFN-g and IL-12Rb2 mRNA expression in TB patients. Our findings suggest that both groups of TB patients may have a similar disregulated pattern of IL-12, IL-10, and IFN-g production during M. tuberculosis infection. Furthermore, the results suggest a potentially pathogenic role for IL-10 in impaired Th1 immune responses in TB patients.