IL-10 neutralization promotes parasite clearance in splenic aspirate cells from patients with visceral leishmaniasis

J Infect Dis. 2011 Oct 1;204(7):1134-7. doi: 10.1093/infdis/jir461.

Abstract

The mechanisms underlying the failure to contain the growth of Leishmania parasites in human visceral leishmaniasis (VL) are not understood. L donovani amastigotes were quantified in cultured splenic aspirate cells to assess the function of IL-10 in lesional tissue ex vivo. In 67 patients with active VL, IL-10 neutralization promoted parasite killing in 73% and complete clearance in 30%, while 18% had more parasites and 9% did not change. The splenic cells secreted increased levels of both tumor necrosis factor α (TNFα) and interferon γ (IFNγ) under IL-10-neutralizing conditions. These findings provide direct support for targeting IL-10 as an approach to therapy in human VL.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / pharmacology
  • Cells, Cultured
  • Child
  • Female
  • Humans
  • Interferon-gamma / metabolism
  • Interleukin-10 / immunology
  • Interleukin-10 / metabolism*
  • Leishmania donovani / drug effects
  • Leishmania donovani / growth & development*
  • Leishmania donovani / immunology
  • Leishmaniasis, Visceral / immunology
  • Leishmaniasis, Visceral / parasitology*
  • Macrophages / metabolism
  • Macrophages / parasitology
  • Male
  • Spleen / metabolism
  • Spleen / parasitology*
  • Tumor Necrosis Factor-alpha / metabolism
  • Young Adult

Substances

  • Antibodies, Monoclonal
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Interferon-gamma