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

José Bordón, Michael W. Plankey, Mary Young, Ruth M. Greenblatt, Maria C. Villacres, Audrey L. French, Jie Zhang, Guy Brock, Savitri Appana, Betsy Herold, Helen Durkin, Jonathan E. Golub, Rafael Fernandez-Botran

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

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 IFNγ 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-4δ2, IL-10, IL-12(p35), IL-13, IL-17A, IFNγ and TNFα 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 6-12months 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.

Original languageEnglish (US)
Pages (from-to)325-331
Number of pages7
JournalCytokine
Volume56
Issue number2
DOIs
StatePublished - Nov 1 2011

    Fingerprint

Keywords

  • Human Immunodeficiency Virus (HIV)
  • Interferonγ (IFNγ)
  • Interleukin-12 (IL-12)
  • Interleukin-4 (IL-4)
  • Tuberculosis (TB)

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Biochemistry
  • Hematology
  • Molecular Biology

Cite this

Bordón, J., Plankey, M. W., Young, M., Greenblatt, R. M., Villacres, M. C., French, A. L., Zhang, J., Brock, G., Appana, S., Herold, B., Durkin, H., Golub, J. E., & Fernandez-Botran, R. (2011). Lower levels of interleukin-12 precede the development of tuberculosis among HIV-infected women. Cytokine, 56(2), 325-331. https://doi.org/10.1016/j.cyto.2011.08.018