A Curative Immune Profile One Week after Treatment of Indian Kala-Azar Patients Predicts Success with a Short-Course Liposomal Amphotericin B Therapy
IR@IICB: CSIR-Indian Institute of Chemical Biology, Kolkata
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| Title |
A Curative Immune Profile One Week after Treatment
of Indian Kala-Azar Patients Predicts Success with a
Short-Course Liposomal Amphotericin B Therapy
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| Creator |
Mondal, Smriti
Bhattacharya, Pradyot Rahaman, Mehebubar Ali, Nahid Goswami, Rama prosad |
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| Subject |
Infectious Diseases and Immunology
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| Description |
The present pilot study investigating the minimum dose for short-course single and double-dose treatment of
kala-azar with an apparently new liposomal formulation of amphotericin B, Fungisome, led to identification of
immunological components for early detection of success and/or failure to cure.Patients were treated with 5, 7.5 (single-dose) and 10 mg/kg body weight (5 mg/kg double-dose) of Fungisome.Immunological investigations involving plasma cytokines and antigen-specific lymphoproliferation and cytokine responses from PBMCs were carried out before, 1 week after Fungisome treatment, at the time of relapse, and again after conventional amphotericin B treatment.
At 1-month follow-up all the patients showed 100% initial cure. However, total doses of 5, 7.5 and 10 mg/kg
Fungisome showed 60%, 50% and 90% cure, respectively, at 6-months posttreatment. Patients successfully cured
demonstrated downregulation of IL-12 and IL-10 in plasma, and two-fold or more elevation of IFN-c, IL-12 and TNF, and
significant down-regulation of IL-10 and TGF-b in culture supernatants 1-week posttreatment irrespective of drug-dose. A differential immune profile, involving insignificant decline in IL-10 and IL-12 in plasma and negligible elevation of IFN-c, IL-
12 and TNF, and persistence of IL-10, despite decline in TGF-b in culture supernatants, in apparently cured individuals,corresponded with relapse within 6-months of treatment.Immunological investigations revealed significant curative and non-curative immunomodulation 1-week
posttreatment, correlating with successful cure and relapse, respectively. Although immune-correlation was doseindependent,almost consistent curative response in patients treated with the highest dose 10 mg/kg reflected a definitiveimpact of the higher-dose on the immune respons
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| Date |
2010
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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/2106/1/PNTD_self.pdf
Mondal, Smriti and Bhattacharya, Pradyot and Rahaman, Mehebubar and Ali, Nahid and Goswami, Rama prosad (2010) A Curative Immune Profile One Week after Treatment of Indian Kala-Azar Patients Predicts Success with a Short-Course Liposomal Amphotericin B Therapy. PLoS Negl Trop Dis, 4 (7). e764.. |
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| Relation |
http://dx.doi:org/10.1371/journal.pntd.0000764
http://www.eprints.iicb.res.in/2106/ |
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