Abstract | OBJECTIVES:
Miltefosine, an orally effective antileishmanial drug, works directly on the parasite by impairing membrane synthesis and subsequent apoptosis of the parasite and has also been reported to have macrophage-activating functions that aid parasite killing. We investigated the type of immunological responses generated in miltefosine-treated Leishmania donovani-infected hamsters, which simulate the clinical situation of human kala-azar. METHODS: RESULTS: By day 45 p.t. there was a significant increase in the mRNA expression of iNOS, IFN-γ, IL-12 and TNF-α, whereas there were significant decreases in IL-4, IL-10 and TGF-β in cured hamsters as compared with their infected counterparts. In vitro stimulation of lymphocytes with concanavalin A and soluble Leishmania donovani antigen showed a maximum LTT response and there was a gradual increase in the NO level (∼7-fold compared with infected counterparts). Anti-Leishmania IgG and IgG1 levels, found to be elevated in the infected group, decreased significantly after treatment but there was a significant increase in IgG2 isotype. CONCLUSIONS: Treatment of Leishmania-infected hamsters with miltefosine reverses the Th2-type response into a strong Th1-type immune response.
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Authors | Reema Gupta, Pramod K Kushawaha, Mukesh Samant, Anil K Jaiswal, Rajendra K Baharia, Anuradha Dube |
Journal | The Journal of antimicrobial chemotherapy
(J Antimicrob Chemother)
Vol. 67
Issue 2
Pg. 440-3
(Feb 2012)
ISSN: 1460-2091 [Electronic] England |
PMID | 22121191
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antibodies, Protozoan
- Antiprotozoal Agents
- Cytokines
- RNA, Messenger
- Phosphorylcholine
- Nitric Oxide
- miltefosine
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Topics |
- Animals
- Antibodies, Protozoan
(blood)
- Antiprotozoal Agents
(administration & dosage)
- Cell Proliferation
- Cricetinae
- Cytokines
(biosynthesis)
- Disease Models, Animal
- Leishmania donovani
(drug effects, immunology)
- Leishmaniasis, Visceral
(drug therapy, immunology)
- Lymphocytes
(immunology)
- Nitric Oxide
(metabolism)
- Phosphorylcholine
(administration & dosage, analogs & derivatives)
- RNA, Messenger
(analysis, genetics)
- Real-Time Polymerase Chain Reaction
- Th1 Cells
(immunology)
- Th2 Cells
(immunology)
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