Therapeutic and immunomodulatory activities of short-course treatment of murine visceral leishmaniasis with KALSOME™10, a new liposomal amphotericin B
IR@IICB: CSIR-Indian Institute of Chemical Biology, Kolkata
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| Title |
Therapeutic and immunomodulatory activities
of short-course treatment of murine visceral leishmaniasis with KALSOME™10, a new liposomal amphotericin B
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| Creator |
Asad, Mohammad
Bhattacharya, Pradyot Banerjee, Antara Banerjee Ali, Nahid |
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| Subject |
Infectious Diseases and Immunology
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| Description |
Visceral leishmaniasis (VL), a potentially fatal disease, is most prevalent in the Indian subcontinent,
East Africa and South America. Since the conventional antileishmanial drugs have many limitations we evaluated a
new ergosterol rich liposomal amphotericin B formulation, KALSOME™10 for its leishmanicidal efficacy, tolerability
and immunomodulatory activity. Normal healthy mice were treated with 3.5 mg/kg single and 7.5 mg/kg single and double doses ofKALSOME™10. Liver and kidney function tests were performed fourteen days after treatment. Next, normal mice were infected with Leishmania donovani amastigotes. Two months post infection they were treated with the above
mentioned doses of KALSOME™10 and sacrificed one month after treatment for estimation of parasite burden in
the liver and spleen by Limiting Dilution Assay. Leishmanial antigen stimulated splenocyte culture supernatants were collected for cytokine detection through ELISA. Flow cytometric studies were performed on normal animals treated with KALSOME™10, Amphotericin B (AmB) and AmBiosome to compare their immunomodulatory activities.
The drug was found to induce no hepato- or nephrotoxicities at the studied doses. Moreover, at all doses,
it led to significant reduction in parasite burden in two month infected BALB/c mice, with 7.5 mg/kg double dose
resulting in almost complete clearance of parasites from both liver and spleen. Interestingly, the drug at 7.5 mg/kg
double dose could almost completely inhibit the secretion of disease promoting cytokines, IL-10 and TGFβ, and
significantly elevate the levels of IFNγ and IL-12, cytokines required for control of the disease. Mice treated with KALSOME™10 showed elevated levels of IFNγ and suppressed IL-10 secretion from both CD4+ and CD8+ subsets
of T cells, as well as from culture supernatants of splenocytes, compared to that of normal, AmB and AmBisome
treated animal Treatment of infected mice with 7.5 mg/kg double dose of KALSOME™10 was safe and effective in
clearing the parasites from the sites of infection. The drug maintains the inherent immunomodulatory activities of
AmB by effectively suppressing disease promoting cytokines IL-10 and TGFβ, thereby boosting IL-12 and IFNγ levels.
This emphasizes KALSOME™10 as a promising drug alternative for lifelong protection from VL.
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| Publisher |
BioMed Central
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| Date |
2015
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| Type |
Article
PeerReviewed |
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| Format |
application/pdf
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| Identifier |
http://www.eprints.iicb.res.in/2104/1/BMC_Infect_Dis_2015_Asad.pdf
Asad, Mohammad and Bhattacharya, Pradyot and Banerjee, Antara Banerjee and Ali, Nahid (2015) Therapeutic and immunomodulatory activities of short-course treatment of murine visceral leishmaniasis with KALSOME™10, a new liposomal amphotericin B. BMC Infectious Diseases, 15. pp. 2-12. |
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| Relation |
http://dx.doi.og/10.1186/s12879-015-0928-6
http://www.eprints.iicb.res.in/2104/ |
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