Servicio de Parasitología y Enfermedad de Chagas, Hospital de Niños Dr. Ricardo Gutiérrez, Buenos Aires, Argentina.
Int Immunopharmacol. 2011 Aug;11(8):1024-31. doi: 10.1016/j.intimp.2011.02.022. Epub 2011 Mar 1.
Heart failure and sudden death are the most common causes of death in patients with Chagas' disease. The main drug available for Chagas treatment is benznidazole, which eradicates Trypanosoma cruzi parasites during the acute stage of infection. However, its effectiveness during the chronic phase remains unclear. Ganglioside GM1 administration in chronically infected patients resulted to be an effective treatment for the cardiac manifestations of Chagas' disease. However, the precise mechanisms of GM1-induced improvement during chronic T. cruzi infection still remain unknown. The aim of the present study was to evaluate the potential benefits of ganglioside GM1 treatment during the chronic stage of murine chagasic infection, analyzing its influence on myocardial pathology as well as its immunomodulatory effects. The results obtained showed that GM1 therapy diminished the extent of myocardial fibrosis induced by T. cruzi in chronically infected mice. In addition, GM1 treatment resulted in a significant reduction in the myocardial expression of the fibrogenic cytokine TGF-β as well as the proinflammatory cytokines and chemokines IFN-γ, TNF-α and CCL5/RANTES. Our experimental data indicate that GM1 could be a promising immunomodulatory agent with capacity to limit the inflammatory process leading to myocardial tissue damage in chronic chagasic patients.
心力衰竭和猝死是恰加斯病患者最常见的死亡原因。治疗恰加斯病的主要药物是苯唑硝唑，它在感染的急性期可消灭克氏锥虫寄生虫。然而，其在慢性期的疗效尚不清楚。在慢性感染的患者中给予神经节苷脂 GM1 治疗，对于恰加斯病的心脏表现是一种有效的治疗方法。然而，GM1 在慢性 T. cruzi 感染期间诱导改善的确切机制仍不清楚。本研究的目的是评估神经节苷脂 GM1 在慢性恰加斯病感染阶段治疗的潜在益处，分析其对心肌病理学的影响及其免疫调节作用。结果表明，GM1 治疗可减轻慢性感染小鼠 T. cruzi 诱导的心肌纤维化程度。此外，GM1 治疗可显著降低心肌中纤维生成细胞因子 TGF-β 以及促炎细胞因子 IFN-γ、TNF-α 和 CCL5/RANTES 的表达。我们的实验数据表明，GM1 可能是一种有前途的免疫调节剂，具有限制导致慢性恰加斯病患者心肌组织损伤的炎症过程的能力。
