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 language | English |
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Pages (from-to) | 747-757 |
Number of pages | 10 |
Journal | Parasitology |
Volume | 131 |
Issue number | 6 |
Early online date | 15 Aug 2005 |
DOIs | |
Publication status | Published - 2005 |
Keywords
- Leishmania donovani
- drug resistance
- glutathione
- sodium stibogluconate