In vitro activity of anti-leishmanial drugs against Leishmania donovani is host cell dependent.


Seifert, K; Escobar, P; Croft, SL; (2010) In vitro activity of anti-leishmanial drugs against Leishmania donovani is host cell dependent. The Journal of antimicrobial chemotherapy, 65 (3). pp. 508-11. ISSN 0305-7453 DOI: 10.1093/jac/dkp500

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Abstract

OBJECTIVES: To evaluate the in vitro activity of anti-leishmanial drugs against intracellular Leishmania donovani amastigotes in different types of macrophages.<br/> METHODS: Mouse peritoneal macrophages (PEMs), mouse bone marrow-derived macrophages (BMMPhi), human peripheral blood monocyte-derived macrophages (PBM Phi) and differentiated THP-1 cells were infected with L. donovani. Cultures were incubated with sodium stibogluconate, amphotericin B deoxycholate (Fungizone), miltefosine or paromomycin sulphate over six concentrations in 3-fold serial dilutions for 5 days. Analysis was based on percentage inhibition of infected macrophages and EC(50)/EC(90) values estimated using sigmoidal curve-fitting.<br/> RESULTS: The rank order of drug activity was the same in the different macrophage populations: amphotericin B > miltefosine > sodium stibogluconate > paromomycin. However, significant (P < 0.05) differences were observed between populations. Amphotericin B was more active in PEMs and BMM Phi (EC(50) 0.02-0.06 microM) compared with PBM Phi and differentiated THP-1 cells (EC(50) 0.08-0.40 microM) and miltefosine was more active in PBM Phi (EC(50) 0.16-0.74 microM) compared with PEMs and BMM Phi (EC(50) 2.60-7.67 microM). Sodium stibogluconate displayed highest activity in PBM Phi (EC(50) 1.38-1.89 microg Sb(v)/mL), followed by PEMs (EC(50) 21.75-27.79 microg Sb(v)/mL) and BMM Phi and differentiated THP-1 cells (EC(50) 28.96-112.77 microg Sb(v)/mL). Paromomycin showed highest activity in PBM Phi (EC(50) 80.03-104.38 microM) and PEMs (EC(50) 75.42-201.63 microM).<br/> CONCLUSIONS: In vitro activity of anti-leishmanial drugs is host cell dependent. This has implications for: (i) the evaluation of in vitro drug activity; (ii) the evaluation of drug susceptibility of clinical isolates; and (iii) the standardization of anti-leishmanial drug assays.<br/>

Item Type: Article
Faculty and Department: Faculty of Infectious and Tropical Diseases > Dept of Immunology and Infection
Research Centre: Antimicrobial Resistance Centre (AMR)
Leishmaniasis Group
Neglected Tropical Diseases Network
PubMed ID: 20089542
Web of Science ID: 274493300023
URI: http://researchonline.lshtm.ac.uk/id/eprint/4237

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