Interleukin 10 responses are associated with sustained CD4 T-cell counts in treated HIV infection

J Infect Dis. 2012 Sep 1;206(5):780-9. doi: 10.1093/infdis/jis380. Epub 2012 Jun 12.

Abstract

Background: Inflammation persists in treated human immunodeficiency virus (HIV) infection and may contribute to an increased risk for non-AIDS-related pathologies. We investigated the correlation of cytokine responses with changes in CD4 T-cell levels and coinfection with hepatitis C virus (HCV) during highly active antiretroviral treatment (HAART).

Methods: A total of 383 participants in the Women's Interagency HIV Study (212 with HIV monoinfection, 56 with HCV monoinfection, and 115 with HIV/HCV coinfection) were studied. HIV-infected women had <1000 HIV RNA copies/mL, 99.7% had >200 CD4 T cells/μL; 98% were receiving HAART at baseline. Changes in CD4 T-cell count between baseline and 2-4 years later were calculated. Peripheral blood mononuclear cells (PBMCs) obtained at baseline were used to measure interleukin 1β (IL-1β), interleukin 6 (IL-6), interleukin 10 (IL-10), interleukin 12 (IL-12), and tumor necrosis factor α (TNF-α) responses to Toll-like receptor (TLR) 3 and TLR4 stimulation.

Results: Undetectable HIV RNA (<80 copies/mL) at baseline and secretion of IL-10 by PBMCs were positively associated with gains in CD4 T-cell counts at follow-up. Inflammatory cytokines (IL-1β, IL-6, IL-12, and TNF-α) were also produced in TLR-stimulated cultures, but only IL-10 was significantly associated with sustained increases in CD4 T-cell levels. This association was significant only in women with HIV monoinfection, indicating that HCV coinfection is an important factor limiting gains in CD4 T-cell counts, possibly by contributing to unbalanced persistent inflammation.

Conclusions: Secreted IL-10 from PBMCs may balance the inflammatory environment of HIV, resulting in CD4 T-cell stability.

Publication types

  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiretroviral Therapy, Highly Active
  • CD4 Lymphocyte Count
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / virology
  • Female
  • HIV Infections / drug therapy
  • HIV Infections / immunology*
  • HIV Infections / virology
  • HIV-1 / immunology*
  • Hepacivirus / immunology*
  • Hepatitis C, Chronic / immunology*
  • Hepatitis C, Chronic / virology
  • Humans
  • Inflammation / immunology
  • Inflammation / virology
  • Interleukin-10 / immunology*
  • Linear Models
  • Multivariate Analysis
  • Prospective Studies
  • RNA, Viral / chemistry
  • RNA, Viral / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Toll-Like Receptor 3 / immunology
  • Toll-Like Receptor 4 / immunology

Substances

  • RNA, Viral
  • TLR3 protein, human
  • TLR4 protein, human
  • Toll-Like Receptor 3
  • Toll-Like Receptor 4
  • Interleukin-10