title: Lower levels of interleukin-12 precede the development of tuberculosis among HIV-infected women.
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.
authors: Department of Medicine, Section of Infectious Diseases, Providence Hospital, and Department of Medicine, Georgetown University Medical Center, Washington, DC, USA. jbordon@provhosp.org
authors: José
authors: J
authors: Bordón
authors: Michael W
authors: MW
authors: Plankey
authors: Mary
authors: M
authors: Young
authors: Ruth M
authors: RM
authors: Greenblatt
authors: Maria C
authors: MC
authors: Villacres
authors: Audrey L
authors: AL
authors: French
authors: Jie
authors: J
authors: Zhang
authors: Guy
authors: G
authors: Brock
authors: Savitri
authors: S
authors: Appana
authors: Betsy
authors: B
authors: Herold
authors: Helen
authors: H
authors: Durkin
authors: Jonathan E
authors: JE
authors: Golub
authors: Rafael
authors: R
authors: Fernandez-Botran
mesh_terms: D018791:CD4 Lymphocyte Count; D005260:Female; D006801:Humans; D018664:Interleukin-12 / Q000097:blood*; D060888:Real-Time Polymerase Chain Reaction; D014376:Tuberculosis / Q000097:blood*
chemical_list: D018664:Interleukin-12