Lower levels of leptin are associated with severity parameters in visceral leishmaniasis patients.

Maria Luciana Silva-Freitas,Anastácio de Queiroz Sousa,Joanna R. Santos-Oliveira,Alda M. Da-Cruz,Aline Mireille da Cunha Fievez

doi:10.1371/journal.pone.0214413

Abstract

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.

Highlights

Visceral leishmaniasis (VL), known as kala-azar, is the most severe clinical form of leishmaniasis due to frequent complications and if untreated, increases the risk of death
The decrease of VL lethality rate should take into account the physician’s knowledge about signs of disease severity and the evaluation of immunological parameters that may be associated with this clinical scenario
Thirty-one VL patients were studied in the active phase, and 22 were prospectively followed up until one month after anti-Leishmania therapy

Summary

Introduction

Visceral leishmaniasis (VL), known as kala-azar, is the most severe clinical form of leishmaniasis due to frequent complications and if untreated, increases the risk of death. For reasons not yet fully understood but that should include the parasite and the effector immune responses, some patients may progress to the more severe forms of the disease, which can be fatal in some cases. In this context, the decrease of VL lethality rate should take into account the physician’s knowledge about signs of disease severity and the evaluation of immunological parameters that may be associated with this clinical scenario

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