Hospital São José de Doenças Infecciosas, Universidade Federal do Ceará, Fortaleza, Brazil.
Laboratório Interdisciplinar de Pesquisas Médicas-Instituto Oswaldo Cruz-FIOCRUZ, Rio de Janeiro, Brazil.
PLoS One. 2019 Mar 26;14(3):e0214413. doi: 10.1371/journal.pone.0214413. eCollection 2019.
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.
内脏利什曼病（VL）是利什曼病中最严重的临床形式，如果不治疗可能致命。它影响免疫系统的重要器官，其特征是特定的免疫抑制，同时伴有强烈的细胞激活和细胞因子风暴。此外，VL 现在被认为是一种全身炎症反应综合征（SIRS），其中多种细胞因子和其他促炎分子被释放。这些炎症介质的作用可能被认为是预后不良和死亡的危险因素。瘦素是一种源自脂肪组织的激素，已在体外和体内利什曼原虫感染模型中被描述具有多种免疫调节功能，特别是增强巨噬细胞杀菌机制。考虑到评估可能与这种临床情况相关的免疫参数可能有助于降低 VL 的致死率，我们评估了瘦素是否与 VL 的发病机制相关。31 名患者在 VL 的活动期被招募，其中 22 名在治疗后一个月（1mpt）进行了随访。除了肌酐水平外，所有临床参数在活动性 VL 患者中均发生改变，特别是白细胞计数和白蛋白和血红蛋白水平。此外，脂多糖（LPS）、免疫球蛋白（Ig）G1 和 G3 抗利什曼原虫和白细胞介素（IL）-6 和 -10 的水平升高高于健康个体。相比之下，活动性 VL 患者表现出血清瘦素水平降低，与白细胞计数以及血红蛋白和白蛋白水平呈正相关。在 1mpt 后，VL 患者的瘦素水平显著升高，达到与健康志愿者相似的水平。正如预期的那样，只有 LPS 水平在 1mpt 后仍升高。这些发现表明，瘦素水平在利什曼原虫感染中受到影响，与与 VL 预后相关的重要参数的相关性表明该分子参与 VL 的免疫发病机制。需要进一步研究评估瘦素作为 VL 预后标志物的可能性。
