内脏利什曼病是新世界国家婴儿利什曼原虫引起的，如果不及时治疗，是最严重且可能致命的利什曼病。目前尚无有效的预防措施，治疗选择也有限。因此，我们研究了已用于治疗乳腺癌的芳香酶抑制剂来曲唑 (LET) 是否具有抗利什曼活性和/或免疫调节潜力，因此可用于治疗婴儿乳杆菌感染。在使用人 THP-1 细胞来源的巨噬细胞的体外感染模型中，LET 对婴儿乳杆菌前鞭毛体和无鞭毛体生命周期阶段具有活性。在离体的人外周血白细胞中，LET 通过经典单核细胞和活化的中性粒细胞减少了婴儿乳杆菌的内化形式。同时，LET 刺激外周血吞噬细胞产生 IL-12/TNF-α，并减少 IL-10/TGF-β 的产生，而在 T 和 B 细胞中，它促进 TNF-α/IFN-γ 的产生并降低了IL-10的水平。在小鼠感染模型中，LET 仅在 5 天后就显着降低了肝脏中的寄生虫负荷，在 15 天后就显着降低了脾脏中的寄生虫负荷。在 LET 体内治疗期间，TNF-α/IFN-γ 的产生也增加。此外，肝脏中发育中肉芽肿的比例减少，成熟肉芽肿的比例增加，而脾脏中器官结构没有显着变化。基于这些数据，LET 的重新定位可能有望用于治疗人类内脏利什曼病。

Visceral leishmaniasis, caused by Leishmania infantum in New World countries, is the most serious and potentially fatal form of leishmaniasis, if left untreated. There are currently no effective prophylactic measures, and therapeutic options are limited. Therefore, we investigated whether the aromatase inhibitor letrozole (LET), which is already used to treat breast cancer, has an antileishmanial activity and/or immunomodulatory potential and therefore may be used to treat L. infantum infection. LET was active against L. infantum promastigote and amastigote life cycle stages in an in vitro infection model using human THP-1 cell-derived macrophages. In human peripheral blood leukocytes ex vivo, LET reduced the internalized forms of L. infantum by classical monocytes and activated neutrophils. Concomitantly, LET stimulated the production of IL-12/TNF-α and decreased the production of IL-10/TGF-β by peripheral blood phagocytes, while in T and B cells, it promoted the production of TNF-α/IFN-γ and decreased that of IL-10. In a murine infection model, LET significantly reduced the parasite load in the liver after just 5 days and in the spleen after 15 days. During in vivo treatment with LET, the production of TNF-α/IFN-γ also increased. In addition, the proportion of developing granulomas decreased and that of mature granulomas increased in the liver, while there was no significant change in organ architecture in the spleen. Based on these data, repositioning of LET may be promising for the treatment of visceral leishmaniasis in humans.