IL-10- and TGF-beta-mediated susceptibility in kala-azar and post-kala-azar dermal leishmaniasis: the significance of amphotericin B in the control of Leishmania donovani infection in India.
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-gamma and IL-12. We address the role of the differential decline of IL-10 and TGF-beta 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-beta 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-gamma and IL-12 production, and elevation of IL-10 and TGF-beta. Cure corresponded with an elevation in IFN-gamma and IL-12 production and down-regulation of IL-10 and TGF-beta. Both CD4(+) and CD8(+) T cells were involved in IFN-gamma and IL-10 production. Interestingly, the retention and maintenance of residual IL-10 and TGF-beta in some SAG-treated individuals and the elevation of IL-10 and TGF-beta 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-beta 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-beta, 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.
Saha
Samiran
S
Infectious Disease and Immunology Division, Indian Institute of Chemical Biology, Kolkata, India.
Mondal
Smriti
S
Ravindran
Rajesh
R
Bhowmick
Swati
S
Modak
Dolanchampa
D
Mallick
Sudeshna
S
Rahman
Mehboobar
M
Kar
Sourjya
S
Goswami
Ramaprasad
R
Guha
Subhasis Kamal
SK
Pramanik
Netai
N
Saha
Bibhuti
B
Ali
Nahid
N
D000293:Adolescent; D000328:Adult; D000666:Amphotericin B / Q000627:therapeutic use*; D000818:Animals; D000967:Antimony Sodium Gluconate / Q000627:therapeutic use; D002478:Cells, Cultured; D018920:Coculture Techniques; D004198:Disease Susceptibility / Q000276:immunology*; D005260:Female; D006801:Humans; D007194:India / Q000453:epidemiology; D016753:Interleukin-10 / Q000502:physiology*; D007893:Leishmania donovani / Q000187:drug effects / Q000276:immunology*; D016773:Leishmaniasis, Cutaneous / Q000188:drug therapy* / Q000453:epidemiology / Q000276:immunology*; D007898:Leishmaniasis, Visceral / Q000188:drug therapy / Q000453:epidemiology / Q000276:immunology*; D008297:Male; D012008:Recurrence; D016212:Transforming Growth Factor beta / Q000502:physiology*
D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D000666:Amphotericin B; D000967:Antimony Sodium Gluconate