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

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.

Unraveling the Role of Leptin in Liver Function and Its Relationship with Liver Diseases

“…Alternatively, ob/ob mice showed higher liver parasite burden when comparing with infected wild-type mice. Moreover, an impaired leptin signaling is linked to a reduction of the innate immune response to Leishmania [ 253 ], and low levels of leptin have been associated with severity parameters in visceral leishmaniasis patients [ 254 ]. Additionally, Trypanosoma cruzi , the etiological agent of Chagas´ disease, also causes an intense inflammatory response within the liver.…”

High Levels of anti-Leishmania IgG3 and Low CD4+ T Cells Count were Associated with Relapses in Visceral Leishmaniasis

“…Finally, we observed that IL-6, a cytokine known to be in ammatory and already associated with a more severe prognosis in the evolution of VL [12,17], was correlated to laboratory severity markers, such as hypoalbuminemia, leukopenia and thrombocytopenia. As expected, C-reactive protein (CRP) levels also correlated positively with IL-6 since its binding with its receptor activates immunocompetent and hematological cells leading to the production of acute phase responses, as CRP [59].…”

“…In parallel, the levels of speci c anti-Leishmania IgG and their subclasses after active VL may have an important role as marker of cure and/or predisposition to relapse [17,53]. Here, IgG3 levels are persistently increased in R-VL group in relation to NR-VL, which may show the presence of continuous parasite stimulation, without a complete control by the immune system.…”

“…Clinical and laboratory markers such as age, bleeding, edema, jaundice, dyspnea, bacterial infection, HIV/AIDS coinfection, leukocyte count below 1500 cells/mm³, thrombocytopenia below 50,000 cells/mm³ and renal failure have also been linked to VL severity [8][9]. Also, several soluble molecules, such as elevated levels of IL-2R, IL-1β, IL-6, IL-8, IL-27, TNF, soluble CD14 (sCD14) [10][11][12][13], soluble CD163 (sCD163) [14] and speci c anti-Leishmania immunoglobulins [15][16], as well as low leptin levels [17] have already been associated with severity of VL. Interestingly, IL-6 levels were also associated with risk of death in VL [12].…”

Impaired Thymic Output Can Be Related to the Low Immune Reconstitution and T Cell Repertoire Disturbances in Relapsing Visceral Leishmaniasis Associated HIV/AIDS Patients

“…Allied to this, elevated levels of lipopolysaccharide (LPS) pointed out that microbial products from the gut lumen translocation, could also be involved in the exacerbated pro-inflammatory status of VL alone (6) and VL/HIV co-infected patients (2,7). Plasma inflammatory cytokines levels, as well as soluble molecules associated with inflammation such as d-dimers, neopterin, soluble CD163 and leptin levels have been described as important predictors of severity and death in VL (8)(9)(10)(11)(12).…”