Laboratory of Immunology and Molecular Biology, University Hospital, Federal University of Sergipe, Aracaju, Brazil.
Health Sciences Graduate Program, Federal University of Sergipe, Aracaju, Brazil.
Front Cell Infect Microbiol. 2022 Nov 24;12:1045668. doi: 10.3389/fcimb.2022.1045668. eCollection 2022.
This investigation aimed to assess the effect of N-acetylcysteine (NAC) as an adjuvant treatment to alleviate visceral leishmaniasis (VL). The present work includes both blinded randomized clinical intervention and experimental studies. The clinical trial included 60 patients with VL randomly allocated into two groups: a test group (n = 30) treated with meglumine antimoniate plus NAC (SbV + NAC) and a control group (n = 30) treated with meglumine antimoniate only (SbV). The primary outcome was clinical cure (absence of fever, spleen and liver sizes reduction, and hematological improvement) in 180 days. The cure rate did not differ between the groups; both groups had similar results in all readout indices. The immunological parameters of the patients treated with SbV + NAC showed higher sCD40L in sera during treatment, and the levels of sCD40L were negatively correlated with Interleukin-10 (IL-10) serum levels. In addition, data estimation showed a negative correlation between the sCD40L levels and the spleen size in patients with VL. For the experiments, peripheral blood mononuclear cells (PBMCs) or PBMC-derived macrophages from healthy donors were exposed to soluble antigen (SLA) or infected with stationary promastigotes of in the presence or absence of NAC. Results revealed that NAC treatment of SLA-stimulated PBMCs reduces the frequency of monocytes producing IL-10 and lowers the frequency of CD4+ and CD8+ T cells expressing (pro-)inflammatory cytokines. Together, these results suggest that NAC treatment may modulate the immune response in patients with VL, thus warranting additional investigations to support its case use as an adjuvant to antimony therapy for VL.
本研究旨在评估 N-乙酰半胱氨酸（NAC）作为辅助治疗减轻内脏利什曼病（VL）的效果。本研究包括盲法随机临床干预和实验研究。临床试验纳入 60 例 VL 患者，随机分为两组：实验组（n=30）给予葡甲胺锑治疗联合 NAC（SbV+NAC），对照组（n=30）给予单纯葡甲胺锑治疗。主要结局为 180 天内临床治愈（无发热、脾脏和肝脏缩小、血液学改善）。两组治愈率无差异；两组在所有观察指标上结果相似。接受 SbV+NAC 治疗的患者的免疫参数显示治疗过程中血清中 sCD40L 更高，且 sCD40L 水平与白细胞介素 10（IL-10）血清水平呈负相关。此外，数据估计显示 VL 患者 sCD40L 水平与脾脏大小呈负相关。对于实验，来自健康供体的外周血单核细胞（PBMC）或 PBMC 衍生的巨噬细胞在存在或不存在 NAC 的情况下暴露于可溶性抗原（SLA）或感染静止期前鞭毛体。结果表明，NAC 处理 SLA 刺激的 PBMC 可降低产生 IL-10 的单核细胞频率，并降低表达（前）炎症细胞因子的 CD4+和 CD8+T 细胞的频率。总之，这些结果表明 NAC 治疗可能调节 VL 患者的免疫反应，因此需要进一步研究来支持其作为 VL 抗锑治疗的辅助治疗。
