Laboratório Interdisciplinar de Pesquisas Médicas, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, Brazil.
Clin Exp Immunol. 2014 Sep;177(3):679-86. doi: 10.1111/cei.12364.
An exacerbated type 1 response to leishmanial antigens is the basis of tissue destruction observed in mucosal leishmaniasis (ML). After therapy, a persistent production of high levels of inflammatory cytokines can confer a poor prognosis. Herein we investigated whether the clinical conditions defined during the active phase of ML affect the magnitude of long-term anti-Leishmania immune response. Twenty clinically cured ML cases were studied. Peripheral blood mononuclear cells (PBMC) were cultured with L. braziliensis antigens (Lb-Ag), Toxoplasma gondii antigens (Tg-Ag), concanavalin-A (Con-A) or medium alone, and the lymphocyte proliferative response and cytokine secretion were quantified. Medical records were reviewed for Montenegro skin test (MST) during diagnosis, duration of ML disease or time elapsed after clinical cure. The duration of disease was correlated positively with MST (r = 0·61). Lb-Ag induced interferon (IFN)-γ was correlated positively with duration of illness (r = 0·69) as well as the frequency of secreting cells [enzyme-linked immunospot (ELISPOT)] assay. No association was observed for Tg-Ag or Con-A. Disease duration was correlated negatively with interleukin (IL)-10 production (r = -0·76). Moreover, a negative correlation between length of time after clinical cure and TNF levels (r = -0·94) or the IFN-γ : IL-10 ratio (r = -0·89) were also seen. We suggest that the magnitude of the IFN-γ inflammatory response triggered by ML can be driven by the time of leishmanial antigens exposition during the active phase of the disease. This pattern could persist even long-term after cure. However, despite IFN-γ levels, the decrease of the TNF and IFN-γ : IL-10 ratio reflects the control of proinflammatory responses achieved by cure of ML, possibly preventing disease relapses.
利什曼原虫抗原引起的 1 型反应加剧是黏膜利什曼病(ML)中观察到的组织破坏的基础。治疗后,高水平炎症细胞因子的持续产生可能预示着预后不良。在此,我们研究了 ML 活动期确定的临床状况是否会影响长期抗利什曼原虫免疫反应的程度。研究了 20 例临床治愈的 ML 病例。用 L. braziliensis 抗原(Lb-Ag)、刚地弓形虫抗原(Tg-Ag)、刀豆蛋白 A(Con-A)或培养基培养外周血单核细胞(PBMC),并定量测定淋巴细胞增殖反应和细胞因子分泌。回顾了 Montenegro 皮肤试验(MST)在诊断时、ML 疾病持续时间或临床治愈后时间的病历。疾病持续时间与 MST 呈正相关(r=0.61)。Lb-Ag 诱导的干扰素(IFN)-γ与疾病持续时间呈正相关(r=0.69),以及分泌细胞的频率[酶联免疫斑点(ELISPOT)]检测。未观察到 Tg-Ag 或 Con-A 的相关性。IL-10 产生与疾病持续时间呈负相关(r=-0.76)。此外,临床治愈后时间与 TNF 水平(r=-0.94)或 IFN-γ:IL-10 比值(r=-0.89)呈负相关。我们认为,由 ML 活动期利什曼原虫抗原暴露时间驱动的 IFN-γ 炎症反应的程度可以持续存在,甚至在治愈后很长时间内也可以持续存在。然而,尽管 IFN-γ 水平降低,但 TNF 和 IFN-γ:IL-10 比值的降低反映了 ML 治愈后对促炎反应的控制,可能防止疾病复发。
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