HIV-1 is not a major driver of increased plasma IL-6 levels in chronic HIV-1 disease

J Acquir Immune Defic Syndr. 2012 Oct 1;61(2):145-52. doi: 10.1097/QAI.0b013e31825ddbbf.


Objective: Increased plasma IL-6 levels have been associated with HIV-1 disease progression risk, yet the drivers of IL-6 production in HIV-1 infection are not known. This study was designed to explore the relationship between HIV-1 replication and IL-6 induction.

Design: Correlations between plasma levels of IL-6 and HIV-1 RNA were examined in 2 clinical studies. To more directly assess the induction of IL-6 by HIV-1, several cell and tissue types that support HIV-1 replication in vivo were infected with HIV-1, and expression of IL-6 was measured.

Methods: Spearman rank correlations were used to examine the relationship between plasma levels of IL-6 and HIV-1 RNA. Macrophages and colonic and lymph node histocultures were infected with HIV-1 or stimulated with bacterial products, lipopolysaccharide (LPS) or flagellin, and IL-6 levels in supernatant were measured by enzyme-linked immunosorbent assay or multiplex bead assay.

Results: In the clinical studies, there was weak or no correlation between plasma levels of IL-6 and HIV-1 RNA, but IL-6 levels were correlated with plasma levels of the LPS coreceptor CD14. Macrophages stimulated with LPS or flagellin showed robust production of IL-6, but there was no increase in IL-6 production after HIV-1 infection. IL-6 expression was not increased in lymph node histocultures obtained from HIV-1-infected subjects nor after productive HIV-1 infection of colonic or lymph node histocultures ex vivo.

Conclusions: We find no evidence that HIV-1 replication is an important driver of IL-6 expression in vivo or in in vitro systems.

Publication types

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

MeSH terms

  • Adult
  • Chronic Disease
  • Cross-Sectional Studies
  • Female
  • HIV Infections / immunology*
  • HIV Infections / virology
  • HIV-1 / growth & development
  • HIV-1 / immunology*
  • HIV-1 / isolation & purification
  • Humans
  • Interleukin-6 / blood*
  • Male
  • Middle Aged
  • Plasma / chemistry
  • Plasma / immunology*
  • RNA, Viral / blood
  • Viral Load*


  • Interleukin-6
  • RNA, Viral