Lower levels of interleukin-12 precede the development of tuberculosis among HIV-infected women

Tuberculosis (TB) is the worldwide leading cause of death among HIV-infected individuals, accounting for more than half of AIDS-related deaths. A high risk of tuberculosis (TB) has been shown in early stages of the HIV disease, even in the presence of normal CD4(+) cell counts. Moreover, the factors that determine protective immunity vs. susceptibility to Mycobacterium tuberculosis cannot be fully explained by simple changes in IFN gamma levels or a shift from Th1 to Th2 cytokines. This work investigated the relationship between cytokine expression profiles in peripheral blood mononuclear cells (PBMC) and susceptibility to M. tuberculosis in 10 HIV+ women who went onto develop TB. RNA transcripts for IL-4, IL-4 delta 2, IL-10, IL-12(p35), 1L-13, IL-17A, IFN gamma and TNF alpha were measured by real-time quantitative PCR in unstimulated or TB peptide antigen-stimulated PBMCs from 10 HIV+ women with positive tuberculin skin tests (TST) and compared with HIV-seropositive and seronegative women without previous TB and negative TST. Stimulated PBMC cultures showed significantly lower expression of IL-12p35 (p = 0.004) and IL-10 (p = 0.026) in the HIV+TB+ group 6-12 months before onset of TB compared to HIV+TB- women. Unstimulated PBMC from HIV+TB+ women also had lower expression of Th2 cytokines [IL-4 (p = 0.056) and IL-13 (p = 0.050)] compared to HIV+TB- women. These results suggest that lower IL-12 production by PBMC in response to TB antigens and lower levels of both Th1 and Th2 cytokines by PBMC correlate with future development of TB in HIV-infected women and may be responsible for their increased susceptibility. (C) 2011 Elsevier Ltd. All rights reserved.