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

Published online by Cambridge University Press:  15 August 2005

K. C. CARTER ,
S. HUTCHISON ,
A. BOITELLE ,
H. W. MURRAY ,
S. SUNDAR  and
A. B. MULLEN
K. C. CARTER
Affiliation:
Department of Immunology, University of Strathclyde, Glasgow, UK
S. HUTCHISON
Affiliation:
Department of Immunology, University of Strathclyde, Glasgow, UK
A. BOITELLE
Affiliation:
Department of Immunology, University of Strathclyde, Glasgow, UK
H. W. MURRAY
Affiliation:
Department of Immunology, University of Strathclyde, Glasgow, UK Department of Medicine, Weill Medical College of Cornell University, New York, USA
S. SUNDAR
Affiliation:
Department of Medicine, Institute of Medical Sciences, Baranas Hindu University, Varansi, India
A. B. MULLEN
Affiliation:
Department Pharmaceutical Sciences, University of Strathclyde, Glasgow, UK
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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.

Keywords

Leishmania donovanisodium stibogluconateglutathionedrug resistance
Type
Research Article
Information
Parasitology , Volume 131 , Issue 6 , December 2005 , pp. 747 - 757
Copyright
© 2005 Cambridge University Press

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