Visceral leishmanicidal activity of hexadecylphosphocholine (miltefosine) in mice deficient in T cells and activated macrophage microbicidal mechanisms Academic Article uri icon

Overview

MeSH Major

  • Antiprotozoal Agents
  • Leishmaniasis, Visceral
  • Macrophage Activation
  • Phosphorylcholine
  • T-Lymphocytes

abstract

  • Hexadecylphosphocholine (miltefosine), a membrane-active alkylphospholipid, may be the first effective oral agent for visceral leishmaniasis, an intracellular protozoal infection of tissue macrophages. In vitro, miltefosine stimulates T cells and macrophages to respond to and secrete activating cytokines, including interferon (IFN)-gamma, and enhances macrophage production of microbicidal reactive nitrogen and oxygen intermediates (RNIs and ROIs, respectively). To determine whether these effects mediate miltefosine's in vivo leishmanicidal efficacy, genetically deficient mice were infected with Leishmania donovani. Intracellular visceral killing was retained in mice lacking or deficient in T cells, endogenous IFN-gamma, and macrophage generation of leishmanicidal RNIs and ROIs. Although mutant mice responded to miltefosine in the absence of tissue granulomas, treatment enhanced granuloma assembly in normal animals. These results suggest that miltefosine's visceral leishmanicidal effect does not require host T cell-dependent or activated macrophage-mediated mechanisms; thus, this agent may potentially be useful in treating T cell-deficient patients with kala-azar.

publication date

  • March 15, 2000

Research

keywords

  • Academic Article

Identity

Language

  • eng

Digital Object Identifier (DOI)

  • 10.1086/315268

PubMed ID

  • 10669380

Additional Document Info

start page

  • 795

end page

  • 9

volume

  • 181

number

  • 2