Human immunodeficiency virus gp120 inhibits interleukin-12 secretion by human monocytes: an indirect interleukin-10-mediated effect

Blood. 1997 Apr 15;89(8):2842-8.

Abstract

Interleukin-12 (IL-12), a cytokine with in vitro and in vivo immunomodulatory effects, is produced mostly by activated monocytes and macrophages. To study the effect of human immunodeficiency virus (HIV) infection on IL-12 production, we investigated the expression of IL-12 at mRNA and protein levels by human monocytes preincubated with HIV-gp120. In these conditions, we show that monocytes have a decreased ability to express IL-12 mRNA subunits and to produce IL-12 p40 and bioactive p70 proteins in response to Staphylococcus aureus strain cowan I (SAC). We showed that in human monocyte cultures, HIV-gp120 induces a significant IL-10 synthesis, which in turn inhibits IL-12 subunits mRNA accumulation and protein secretion after SAC-activation. Similar data were obtained with human macrophages. These results suggest that, during HIV infection, gp120 induces in uninfected monocytes and macrophages IL-10/IL-12 disregulation, which can alter immune response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • HIV Envelope Protein gp120 / pharmacology*
  • HIV-1 / physiology*
  • Humans
  • Interleukin-10 / physiology*
  • Interleukin-12 / biosynthesis
  • Interleukin-12 / genetics
  • Interleukin-12 / metabolism*
  • Leukocytes, Mononuclear / drug effects*
  • Leukocytes, Mononuclear / metabolism
  • Lymphocyte Activation
  • Macrophages / physiology
  • Polymerase Chain Reaction
  • RNA, Messenger / biosynthesis

Substances

  • HIV Envelope Protein gp120
  • RNA, Messenger
  • Interleukin-10
  • Interleukin-12