Sodium stibogluconate resistance in leishmania donovani correlates with greater tolerance to macrophage antileishmanial responses and trivalent antimony therapy

K.C. Carter, S. Hutchison, A. Boitelle, H.W. Murray, S. Sundar, A. Mullen

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Abstract

Co-treatment of mice infected with different strains of Leishmania donovani with a non-ionic surfactant vesicle formulation of buthionine sulfoximine (BSO-NIV), and sodium stibogluconate (SSG), did not alter indicators of Th1 or Th2 responses but did result in a significant strain-independent up-regulation of IL6 and nitrite levels by stimulated splenocytes from treated mice compared to controls. The efficacy of BSO-NIV/SSG treatment was dependent on the host being able to mount a respiratory burst indicating that macrophages are important in controlling the outcome of treatment. In vitro studies showed that SSG resistance was associated with a greater resistance to killing by activated macrophages, treatment with hydrogen peroxide or potassium antimony tartrate. Longitudinal studies showed that a SSG resistant (SSG-R) strain was more virulent than a SSG susceptible (SSG-S) strain, resulting in significantly higher parasite burdens by 4 months post-infection. These results indicate that SSG exposure may favour the emergence of more virulent strains.

Original languageEnglish
Pages (from-to)747-757
Number of pages10
JournalParasitology
Volume131
Issue number6
Early online date15 Aug 2005
DOIs
Publication statusPublished - 2005

Keywords

  • Leishmania donovani
  • drug resistance
  • glutathione
  • sodium stibogluconate

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