Furthermore, stimulation of PBMC isolated from VL patients with rLdcTXN resulted in up-regulation of IL-4 and IL-10 production whereas IL-12 and IFN-γ was significantly down-regulated suggesting a pivotal role of cTXN in provoking the immune suppression during VL.
We performed combined blockade of IFN-γ and TNF-α in VL splenic biopsies and demonstrated it's impact on number of viable amastigotes and cytokine production.
To extend testing the therapeutic effects of applying IL-10 receptor (IL-10R) blockade with antileishmanial chemotherapy, BALB/c mice with established intracellular Leishmania donovani infection were injected once with anti-IL-10R mAb at the time low-dose, daily pentavalent antimony (Sb) therapy was initiated.
Immunization with rLdp45 exerted considerable prophylactic efficacy (∼85%) supported by an increase in mRNA expression of iNOS, IFN-γ, TNF-α and IL-12 and decrease in TGF-β and IL-4, indicating its potential as a vaccine candidate against VL.
In addition, PBMCs collected from treated and untreated mucosal leishmaniasis (ML) and visceral leishmaniasis (VL) patients, as well as in healthy subjects living in endemic region of disease, were in vitro stimulated, when IFN-γ, IL-4 and IL-10 levels were evaluated in the cell supernatant.
These results indicate the production of IL-10 during L. donovani infection, and suggest a role for this cytokine in the regulation of immune responsiveness during visceral leishmaniasis.
Most importantly, blockade of IFNγ in ex-vivo splenic aspirate cultures demonstrated that despite the progressive nature of their disease, the endogenous IFNγ produced in patients with active VL serves to limit parasite growth.
The stimulation of peripheral blood mononuclear cells with r-LdODC up-regulated IL-10 production but not IFN-γ production from CD4(+) T cells in active as well as cured visceral leishmaniasis cases, indicating a pivotal role for r-LdODC in causing strong immune suppression in a susceptible host.
Thus, an aberrant activation of the TNF system with possible negative immunological and virological consequences is present in HIV-1-infected patients with VL.
Visceral leishmaniasis (VL) is associated with increased circulating levels of multiple pro-inflammatory cytokines and chemokines, including IL-12, IFNγ, and TNFα, and elevated expression of IFNγ mRNA in lesional tissue such as the spleen and bone marrow.
At VL diagnosis, co-infected patients showed higher serum levels of interferon-gamma (IFN-gamma) than matched HIV-1 controls without VL, and lower serum concentrations of IL-10 than non-immunocompromised VL controls.
This paper examines the IL-2, IFN-γ, IFN-γ-induced protein 10 (IP-10), and monokine-induced-by-IFN-γ (MIG) levels in whole blood-stimulated <i>in vitro</i> with soluble <i>Leishmania</i> antigen (SLA)-taken from asymptomatic individuals and patients treated for VL living in a post-outbreak (<i>Leishmania infantum</i>) area in Spain, and in an endemic (<i>Leishmania donovani</i>) area of Bangladesh.
Efficacy against VL was mediated by a CD4<sup>+</sup>TNF-α T lymphocyte response against the NH36-F3 domain, while against tegumentary leishmaniasis (TL) a CD8<sup>+</sup> T lymphocyte response to F1 was also required.
Results indicated that the administration of live recombinant Leishmania produced a significant high level of IFN-γ accompanied by reduced levels of IL-10 as compared to wild-type parasites as live vaccine control, thus suggesting the induction of a Th1-type immune response in a mouse model of visceral leishmaniasis.
Analyses showed that the distribution of TNFA RFLP alleles (TNF1 and TNF2) and the TNF MSM alleles (TNFa1 to TNFa15) differed between individuals with VL and those with DTH+ phenotypes.
In addition, PBMCs collected from treated and untreated mucosal leishmaniasis (ML) and visceral leishmaniasis (VL) patients, as well as in healthy subjects living in endemic region of disease, were in vitro stimulated, when IFN-γ, IL-4 and IL-10 levels were evaluated in the cell supernatant.