Dataset Information

The Severity of Visceral Leishmaniasis Correlates with Elevated Levels of Serum IL-6, IL-27 and sCD14.

ABSTRACT:

Background

Visceral leishmaniasis (VL) is a severe disease caused by infection with protozoa of the genus Leishmania. Classic VL is characterized by a systemic infection of phagocytic cells and an intense activation of the inflammatory response. It is unclear why 90% of infected individuals do not develop the disease while a minority develop the classical form. Furthermore, among those that develop disease, a small group progresses to more severe form that is unresponsive to treatment. The presence of inflammatory mediators in serum could theoretically help to control the infection. However, there is also a release of anti-inflammatory mediators that could interfere with the control of parasite multiplication. In this study, we took advantage of the spectrum of outcomes to test the hypothesis that the immune profile of individuals infected with Leishmania (L.) infantum is associated with the development and severity of disease.

Methodology/principal findings

Sera from patients with confirmed diagnosis of VL were evaluated for the presence of numerous molecules, and levels compared with healthy control and asymptomatic infected individuals.

Conclusions/principal findings

Although differences were not observed in LPS levels, higher levels of sCD14 were detected in VL patients. Our data suggest that L. infantum may activate the inflammatory response via CD14, stimulating a generalized inflammatory response with production of several cytokines and soluble molecules, including IFN-?, IL-27, IL-10, IL-6 and sCD14. These molecules were strongly associated with hepatosplenomegaly, neutropenia and thrombocytopenia. We also observed that IL-6 levels greater than 200 pg/ml were strongly associated with death. Together our data reinforce the close relationship of IFN-?, IL-10, IL-6, TNF-? and IL-27 in the immune dynamics of VL and suggest the direct participation of sCD14 in the activation of the immune response against L. infantum.

SUBMITTER: Dos Santos PL

PROVIDER: S-EPMC4729473 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature

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Publications

The Severity of Visceral Leishmaniasis Correlates with Elevated Levels of Serum IL-6, IL-27 and sCD14.

Dos Santos Priscila L PL de Oliveira Fabrícia A FA Santos Micheli Luize B ML Cunha Luana Celina S LC Lino Michelle T B MT de Oliveira Michelle F S MF Bomfim Manuela O M MO Silva Angela Maria AM de Moura Tatiana R TR de Jesus Amélia R AR Duthie Malcolm S MS Reed Steven G SG de Almeida Roque P RP

PLoS neglected tropical diseases 20160127 1

<h4>Background</h4>Visceral leishmaniasis (VL) is a severe disease caused by infection with protozoa of the genus Leishmania. Classic VL is characterized by a systemic infection of phagocytic cells and an intense activation of the inflammatory response. It is unclear why 90% of infected individuals do not develop the disease while a minority develop the classical form. Furthermore, among those that develop disease, a small group progresses to more severe form that is unresponsive to treatment. T ...[more]

PMID: 26814478

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Project description:Visceral leishmaniasis (VL) is the most severe clinical form of leishmaniasis, and if untreated may be fatal. It affects important organs of the immune system and is characterized by a specific immunosuppression, along with intense cellular activation and cytokine storm. Moreover, VL is now recognized as a systemic inflammatory response syndrome (SIRS), in which multiple cytokines and other pro-inflammatory molecules are released. The action of these inflammatory mediators may be considered risk factors for poor prognosis and death. Leptin, a hormone derived from adipose tissue, has been described with several immunoregulatory functions in vitro and in vivo Leishmania infection models, particularly for enhancing the macrophage microbicidal mechanisms. Considering that evaluation of immunologic parameters that may be associated with this clinical scenario may help to decrease VL lethality, we evaluated whether leptin is associated with VL pathogenesis. Thirty-one patients were recruited in the active phase of VL, of which 22 were followed up until one month after therapy (1mpt). Except for creatinine levels, all clinical parameters were altered in active VL patients, especially leucocyte counts and albumin and hemoglobin levels. Also, elevated levels of lipopolysaccharide (LPS), immunoglobulins (Ig)G1 and G3 anti-Leishmania and interleukins (IL)-6 and -10 were higher than in healthy individuals. In contrast, active VL patients presented diminished serum leptin levels and positive correlation with leukocytes counts and hemoglobin and albumin levels. After 1mpt, VL patients showed a significant increase in leptin levels, reaching values similar to healthy volunteers. As expected, only LPS levels remained elevated after 1mpt. These findings suggest that leptin levels are affected in Leishmania infection and the correlation with important parameters associated with the prognosis of VL points to the involvement of this molecule in VL immunopathogenesis. Additional studies are needed to evaluate the possibility of leptin as a prognostic marker of VL.

Project description:Introduction:To sustain the achievement of kala-azar elimination program (KEP), early detection and treatment of the visceral leishmaniasis (VL) cases and associated modalities such as treatment failure (TF), relapse VL (RVL), and Post-kala-azar dermal leishmaniasis (PKDL) is the cornerstone. A predictive biomarker for VL development and related complications could also play a crucial role in curtailing disease incidence and transmission. Investigations to find a biomarker with prospective capabilities are, however, scarce. Using samples and known clinical outcomes generated within two previous longitudinal cohort studies, we aimed to determine if fluctuations in serum anti-rK39 antibody levels could provide such predictive value. Materials and Methods:Serum samples collected at four different time points (Baseline, 12, 18, and 24 months) from 16 patients who had developed VL within the monitoring period and 15 of their asymptomatic healthy controls counterparts were investigated. To investigate potential prediction of VL related complications, serum samples of 32 PKDL, 10 RVL, 07 TF, and 38 cured VL from a single dose AmBisome trial were analyzed. Of this second panel, all patients were monitored for 5 years and sera were collected at four time points (Baseline then 1, 6, and 12 months after treatment). The level of anti-rK39 antibodies in archived samples was measured by a semi-quantitative ELISA. Results:The mean antibody level was significantly higher in VL patients compared to their asymptomatic healthy counterparts at each time point. Likewise, we observed a trend toward elevations in antibody levels for PKDL, RVL, TF relative to the reducing levels observed in cured VL. Receiver operating characteristic (ROC) analysis found a promising predictive power of rK39 antibody levels to reveal progression from asymptomatic Leishmania donovani infection stage to VL, defined as 87.5% sensitive and 95% specific. Following treatment, rk39 antibody notably showed 100% sensitivity and 95% specificity in predicting TF. Conclusion:Our data indicate that the relative quantity of serum anti-rK39 antibody has promise within either a predictive or prognostic algorithm for VL and VL-related modalities. These could enable VL control programs to implement more effective measures to eliminate the disease. Further research is, however, imperative to standardize the rK39 antibody ELISA between sites prior to broader use.

Dataset Information

The Severity of Visceral Leishmaniasis Correlates with Elevated Levels of Serum IL-6, IL-27 and sCD14.

Background

Methodology/principal findings

Conclusions/principal findings

Publications

The Severity of Visceral Leishmaniasis Correlates with Elevated Levels of Serum IL-6, IL-27 and sCD14.

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