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Post kala-azar dermal leishmaniasis (PKDL), a dermal sequel of visceral leishmaniasis presents with macular or polymorphic lesions. As immunological variations between these two forms have not been delineated, we evaluated levels of antileishmanial total Ig, IgG and its subclasses, IgM, IgE, IgG avidity, cytokines IL-10, IL-4, IL-13 and expression of CD19. The levels of Ig and IgG in polymorphic PKDL were higher than macular PKDL, while significant curtailment in levels of Ig, IgM and IgG following treatment was evident only in polymorphic PKDL. With regard to IgG subclasses, IgG1 and IgG3 were significantly raised in polymorphic PKDL, whereas in macular PKDL only IgG1 was elevated; treatment decreased levels of IgG1, IgG2 and IgG3 only in polymorphic PKDL; IgE levels were raised in both groups but no marked alterations occurred following treatment. The avidity of IgG was higher in polymorphic PKDL and correlated with duration of disease. IL-10 was higher in polymorphic PKDL and decreased significantly after treatment, whereas in macular PKDL IL-4 predominated. Taken together, in PKDL the humoral immune response was greater in the polymorphic variant than the macular form suggesting that serological markers may have a role in monitoring polymorphic PKDL., (Copyright © 2012 Royal Society of Tropical Medicine and Hygiene. Published by Elsevier Ltd. All rights reserved.)

Background: The increasing incidence of unresponsiveness to antimonials in leishmaniasis prompted the use of newer drugs such as miltefosine. Miltefosine influences macrophage effector functions, but its effect on patients with post kala-azar dermal leishmaniasis (PKDL) has not been evaluated., Methodology: The immunomodulatory activity of miltefosine was evaluated in patients with PKDL by studying the expression of activation markers (CD14 and CD16) and costimulatory molecules (CD80 and CD86) on circulating monocytes, levels of pro-inflammatory cytokines (tumor necrosis factor α, interleukin 6, interleukin 1β, and interleukin 8) and anti-inflammatory cytokines (interleukin 10, transforming growth factor β, interleukin 4, and interleukin 13) in serum and peripheral blood mononuclear cell culture supernatants, and serum nitrite and arginase activity., Results: Miltefosine on circulating monocytes upregulated expression of CD16 and CD86 and reduced that of CD14. Miltefosine also induced a significant increase in circulating levels of pro-inflammatory cytokines with a concomitant decrease in anti-inflammatory cytokines. Its macrophage activating potential was evidenced by its ability to decrease serum arginase activity and increase serum nitrite., Conclusions: Miltefosine increased the proportion of monocytes that have a pro-inflammatory phenotype, which was accompanied by an enhanced secretion of pro-inflammatory cytokines and increased levels of serum nitrite. The decrease in anti-inflammatory cytokine levels and serum arginase activity collectively indicated that miltefosine triggered a robust T-helper 1 response that facilitated parasite elimination.

Background: Post-kala-azar dermal leishmaniasis (PKDL), an established sequela of visceral leishmaniasis (VL), is proposed to facilitate anthroponotic transmission of VL, especially during interepidemic periods. Immunopathological mechanisms responsible for Indian PKDL are still poorly defined., Methods: Our study attempted to characterize the immune profiles of patients with PKDL or VL relative to that of healthy control subjects by immunophenotyping, intracellular cytokine staining of peripheral blood mononuclear cells, and enzyme-linked immunosorbent assay for serum cytokines and immunoglobulin G (IgG) subclasses., Results: Patients with PKDL had significantly raised percentages of peripheral CD3+CD8+ cells compared with control subjects, a difference that persisted after cure. Patients with PKDL showed an intact response to phytohemagglutinin, with the percentages of lymphocytes expressing interferon (IFN)-gamma, interleukin (IL)-2, IL-4, and IL-10 being comparable to those in control subjects. Patients with VL had decreased IFN-gamma and IL-2 expression, which was restored after cure, and increased IL-10 expression, which persisted after cure. In their response to Leishmania donovani antigen, patients with PKDL showed a 9.6-fold increase in the percentage of IL-10-expressing CD3+CD8+ lymphocytes compared with control subjects, and this percentage decreased with treatment. Patients with PKDL had raised levels of IgG3 and IgG1 (surrogate markers for IL-10), concomitant with increased serum levels of IL-10., Conclusions: IL-10-producing CD3+CD8+ lymphocytes are important protagonists in the immunopathogenesis of Indian PKDL.