印度黑热病患者治疗一周后具有治愈性免疫特征，预示着采用短程脂质体两性霉素 B 治疗可取得成功。
A curative immune profile one week after treatment of Indian kala-azar patients predicts success with a short-course liposomal amphotericin B therapy.
机构信息
Infectious Diseases and Immunology Division, Indian Institute of Chemical Biology, Kolkata, India.
出版信息
PLoS Negl Trop Dis. 2010 Jul 27;4(7):e764. doi: 10.1371/journal.pntd.0000764.
BACKGROUND
The present pilot study investigating the minimum dose for short-course single and double-dose treatment of kala-azar with an apparently new liposomal formulation of amphotericin B, Fungisome, led to identification of immunological components for early detection of success and/or failure to cure.
METHODS
Patients were treated with 5, 7.5 (single-dose) and 10 mg/kg body weight (5 mg/kg double-dose) of Fungisome. Immunological investigations involving plasma cytokines and antigen-specific lymphoproliferation and cytokine responses from PBMCs were carried out before, 1 week after Fungisome treatment, at the time of relapse, and again after conventional amphotericin B treatment.
RESULTS
At 1-month follow-up all the patients showed 100% initial cure. However, total doses of 5, 7.5 and 10 mg/kg Fungisome showed 60%, 50% and 90% cure, respectively, at 6-months posttreatment. Patients successfully cured demonstrated downregulation of IL-12 and IL-10 in plasma, and two-fold or more elevation of IFN-gamma, IL-12 and TNF, and significant down-regulation of IL-10 and TGF-beta in culture supernatants 1-week posttreatment irrespective of drug-dose. A differential immune profile, involving insignificant decline in IL-10 and IL-12 in plasma and negligible elevation of IFN-gamma, IL-12 and TNF, and persistence of IL-10, despite decline in TGF-beta in culture supernatants, in apparently cured individuals, corresponded with relapse within 6-months of treatment.
CONCLUSION
Immunological investigations revealed significant curative and non-curative immunomodulation 1-week posttreatment, correlating with successful cure and relapse, respectively. Although immune-correlation was dose-independent, almost consistent curative response in patients treated with the highest dose 10 mg/kg reflected a definitive impact of the higher-dose on the immune response. TRIAL REGISTRATION NAME AND NUMBER: Clinical Trials Registry--India (CTRI) CTRI/2009/091/000764.
背景
本初步研究旨在探讨新型脂质体制剂两性霉素 B（Fungisome）短程单剂量和双剂量治疗黑热病的最小剂量，研究结果确定了免疫相关指标，可用于早期检测治疗成功和/或失败。
方法
患者接受 5、7.5（单剂量）和 10mg/kg 体重（双剂量 5mg/kg）Fungisome 治疗。在 Fungisome 治疗前、治疗后 1 周、复发时以及再次接受常规两性霉素 B 治疗后，进行涉及血浆细胞因子、抗原特异性淋巴细胞增殖和 PBMC 细胞因子反应的免疫学研究。
结果
在 1 个月的随访中，所有患者均获得了 100%的初始治愈。然而，6 个月的随访显示，Fungisome 的总剂量为 5、7.5 和 10mg/kg 时，治愈率分别为 60%、50%和 90%。成功治愈的患者在治疗后 1 周时表现出血浆中 IL-12 和 IL-10 的下调，以及 IFN-γ、IL-12 和 TNF 的两倍或更多升高，以及培养上清液中 IL-10 和 TGF-β的显著下调，而与药物剂量无关。在治疗后 6 个月内复发的患者中，免疫谱存在差异，即血浆中 IL-10 和 IL-12 无明显下降，IFN-γ、IL-12 和 TNF 升高不明显，尽管培养上清液中 TGF-β下降，但 IL-10 仍持续存在。
结论
免疫研究显示，治疗后 1 周时的显著治愈和非治愈免疫调节与成功治愈和复发分别相关。尽管免疫相关性与剂量无关，但在接受最高剂量 10mg/kg 治疗的患者中几乎一致的治愈反应反映了更高剂量对免疫反应的明确影响。
试验注册名称和编号
印度临床试验注册中心（CTRI）CTRI/2009/091/000764。
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