Cutaneous leishmaniasis (CL) due to L. braziliensis is associated with an exaggerated inflammatory response and tissue damage. Miltefosine is more effective than pentavalent antimony (Sb^v) in the treatment of CL, and here, we evaluate the ability of Sb^v, miltefosine, and GM-CSF administered intravenously, orally, or topically, respectively, to modify the immune response. Patients were treated with miltefosine plus GM-CSF, miltefosine plus placebo, or Sb^v. Mononuclear cells were stimulated with soluble Leishmania antigen (SLA) on day 0 and day 15 of therapy, and cytokine levels were determined in supernatants by ELISA. The lymphocyte proliferation and oxidative burst were evaluated by flow cytometry, and the degree of infection and Leishmania killing by optical microscopy. Proliferation of CD4⁺ T cells were enhanced in patients using miltefosine and in CD8⁺ T cells when GM-CSF was associated. Enhancement in the oxidative burst occurred in the miltefosine plus GM-CSF group on day 15 of therapy. Moreover, the number of L. braziliensis in infected monocytes on day 15 as well as the percentage of infected cells was lower after 48- and 72-hour culture in cells from patients treated with miltefosine plus GM-CSF. In addition to the ability of miltefosine to kill Leishmania, the changes in the immune response caused by miltefosine and GM-CSF may increase the cure rate of CL patients using these drugs.

中文翻译：

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米非福辛联合局部GM-CSF调节皮肤利什曼病患者免疫应答的能力评估。

由于巴西乳杆菌引起的皮肤利什曼病（CL）与过度的炎症反应和组织损伤有关。Miltefosine在CL的治疗中比五价锑（Sb ^v）更有效，在这里，我们评估了分别通过静脉，口服或局部给药的Sb ^v，miltefosine和GM-CSF改变免疫应答的能力。患者接受米非福星加GM-CSF，米非福星加安慰剂或Sb ^v治疗。可溶性利什曼原虫刺激单核细胞在治疗的第0天和第15天检测抗原（SLA），并通过ELISA测定上清液中的细胞因子水平。通过流式细胞术评估淋巴细胞的增殖和氧化爆发，并通过光学显微镜观察感染的程度和利什曼原虫的杀死。使用miltefosine的患者和结合GM-CSF的CD8 ⁺ T细胞的CD4 ⁺ T细胞的增殖均得到增强。在治疗的第15天，米非福新加GM-CSF组的氧化爆发增强。此外，在接受米替福辛+治疗的患者的细胞中培养48和72小时后，第15天感染的单核细胞中的巴西乳杆菌数量以及感染细胞的百分比较低。GM-CSF。除了米替福星杀死利什曼原虫的能力外，由米替福星和GM-CSF引起的免疫反应的改变可能会提高使用这些药物的CL患者的治愈率。