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

  • K. C. CARTER (a1), S. HUTCHISON (a1), A. BOITELLE (a1), H. W. MURRAY (a1) (a2), S. SUNDAR (a3) and A. B. MULLEN (a4)...

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.

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Corresponding author

Department of Immunology, SIBS, University of Strathclyde, 31 Taylor Street, Glasgow G4 0NR, UK. Tel: +44 0141 548 3823. Fax: +44 0141 548 3427. E-mail: k.carter@strath.ac.uk

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