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IL-10- and TGF-�-Mediated Susceptibility in Kala-azar and Post-kala-azar Dermal Leishmaniasis: The Significance of Amphotericin B in the Control of Leishmania donovani Infection in India1

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Title IL-10- and TGF-�-Mediated Susceptibility in Kala-azar and
Post-kala-azar Dermal Leishmaniasis: The Significance of
Amphotericin B in the Control of Leishmania donovani
Infection in India1
 
Creator Saha, Samiran
Mondal, Smriti
Ravindran, Rajesh
Bhowmick, Swati
Modak, Dolanchampa
Mallick, Sudeshna
Rahman, Mehboobar
Kar, Sourjya
Goswami, Rama prosad
Guha, Subhasis Kamal
Pramanik, Netai
Saha, Bibhuti
Ali, Nahid
 
Subject Infectious Diseases and Immunology
 
Description Visceral leishmaniasis (VL) or kala-azar is known to be associated with a mixed Th1-Th2 response, and effective host defense
requires the induction of IFN-� and IL-12. We address the role of the differential decline of IL-10 and TGF-� in response to
sodium antimony gluconate (SAG) and amphotericin B (AmB), the therapeutic success of SAG and AmB in Indian VL, and the
significance of IL-10 and TGF-� in the development and progression of post-kazla-azar dermal leishmaniasis (PKDL). In the
active disease, PBMC from VL patients showed suppressed Ag-specific lymphoproliferation, IFN-� and IL-12 production, and
elevation of IL-10 and TGF-�. Cure corresponded with an elevation in IFN-� and IL-12 production and down-regulation of IL-10
and TGF-�. Both CD4� and CD8� T cells were involved in IFN-� and IL-10 production. Interestingly, the retention and maintenance
of residual IL-10 and TGF-� in some SAG-treated individuals and the elevation of IL-10 and TGF-� in PKDL, a sequel
to kala-azar, probably reflects the role of these cytokines in reactivation of the disease in the form of PKDL. Contrastingly, AmB
treatment of VL resulted in negligible TGF-� levels and absolute elimination of IL-10, reflecting the better therapeutic activity of
AmB and its probable role in the recent decline in PKDL occurrences in India. Moreover, elucidation of immune responses in
Indian PKDL patients revealed a spectral pattern of disease progression where disease severity could be correlated inversely with
lymphoproliferation and directly with TGF-�, IL-10, and Ab production. In addition, the enhancement of CD4�CD25� T cells in
active VL, their decline at cure, and reactivation in PKDL suggest their probable immunosuppressive role in these disease
forms. The Journal of Immunology, 2007, 179: 5592–5603.
 
Date 2007
 
Type Article
PeerReviewed
 
Format application/pdf
 
Identifier http://www.eprints.iicb.res.in/266/1/JOURNAL_OF_IMMUNOLOGY%2C_179(_8)%2C_5592%2D5603%2C2007[26].pdf
Saha, Samiran and Mondal, Smriti and Ravindran, Rajesh and Bhowmick, Swati and Modak, Dolanchampa and Mallick, Sudeshna and Rahman, Mehboobar and Kar, Sourjya and Goswami, Rama prosad and Guha, Subhasis Kamal and Pramanik, Netai and Saha, Bibhuti and Ali, Nahid (2007) IL-10- and TGF-�-Mediated Susceptibility in Kala-azar and Post-kala-azar Dermal Leishmaniasis: The Significance of Amphotericin B in the Control of Leishmania donovani Infection in India1. The Journal of Immunology, 179 (8). pp. 5592-5603.
 
Relation http://dx.doi.org/10.179;5592-5603
http://www.eprints.iicb.res.in/266/