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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.
J Immunol. 2007 Oct 15; 179(8):5592-603.JI

Abstract

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.

Authors+Show Affiliations

Infectious Disease and Immunology Division, Indian Institute of Chemical Biology, Kolkata, India.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17911647

Citation

Saha, Samiran, et al. "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." Journal of Immunology (Baltimore, Md. : 1950), vol. 179, no. 8, 2007, pp. 5592-603.
Saha S, Mondal S, Ravindran R, et al. 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. J Immunol. 2007;179(8):5592-603.
Saha, S., Mondal, S., Ravindran, R., Bhowmick, S., Modak, D., Mallick, S., Rahman, M., Kar, S., Goswami, R., Guha, S. K., Pramanik, N., Saha, B., & Ali, N. (2007). 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. Journal of Immunology (Baltimore, Md. : 1950), 179(8), 5592-603.
Saha S, et al. 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. J Immunol. 2007 Oct 15;179(8):5592-603. PubMed PMID: 17911647.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Saha,Samiran, AU - Mondal,Smriti, AU - Ravindran,Rajesh, AU - Bhowmick,Swati, AU - Modak,Dolanchampa, AU - Mallick,Sudeshna, AU - Rahman,Mehboobar, AU - Kar,Sourjya, AU - Goswami,Ramaprasad, AU - Guha,Subhasis Kamal, AU - Pramanik,Netai, AU - Saha,Bibhuti, AU - Ali,Nahid, PY - 2007/10/4/pubmed PY - 2007/12/6/medline PY - 2007/10/4/entrez SP - 5592 EP - 603 JF - Journal of immunology (Baltimore, Md. : 1950) JO - J Immunol VL - 179 IS - 8 N2 - 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. SN - 0022-1767 UR - https://www.unboundmedicine.com/medline/citation/17911647/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_ L2 - http://www.jimmunol.org/cgi/pmidlookup?view=long&pmid=17911647 DB - PRIME DP - Unbound Medicine ER -