Laboratório de Parasitologia, Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto FCFRP-USP, Universidade de São Paulo, Avenida do Café s/no, 14040-903 Ribeirão Preto, SP, Brasil.
Immunobiology. 2010 Dec;215(12):980-6. doi: 10.1016/j.imbio.2009.11.002. Epub 2010 Feb 16.
A significant role for hormones in regulating the balance of Th1- and Th2-associated cytokines with a role in modulating diseases has been accumulating. Previously, we reported that dehydroepiandrosterone (DHEA), the most abundant steroid hormone synthesized by the adrenal cortex, markedly reduced the blood and tissue parasites in experimentally Trypanosoma cruzi-infected rats. Based on these findings, the main purpose of this study was to investigate the effect of dehydroepiandrosterone-sulfate ester (DHEA-S) therapy alone or in combination with benznidazole (BNZ) (recommended in Brazil for the treatment of T. cruzi infection) will be effective during the acute phase of two different lineages of T. cruzi strains: type I (Y strain) and type II (Bolivia strain) of T. cruzi. Administration of either DHEA-S or BNZ alone or in combination significantly reduced the Y strain parasite load as compared with untreated. Furthermore treatment with DHEA-S resulted in Bolivia strain clearance. This protective effect of DHEA-S was associated with the host's immune response, as evidence by enhanced levels of interferon-gamma and interleukin-2. DHEA-S treatment also increased peritoneal macrophages levels and nitrite production. DHEA-S treatment was effective in reducing the mortality rate as compared to BNZ alone or to combiner DHEA-S+BNZ treatment of T. cruzi Bolivia strain infected animals. These findings suggest that hormonal therapy may have a protective effect in the treatment of T. cruzi infection.
激素在调节 Th1 和 Th2 相关细胞因子平衡方面发挥着重要作用，其在调节疾病方面的作用也在逐渐积累。此前，我们曾报道过，脱氢表雄酮（DHEA）是肾上腺皮质合成的最丰富的类固醇激素，它能显著降低实验性感染克氏锥虫的大鼠的血液和组织寄生虫。基于这些发现，本研究的主要目的是研究单独使用脱氢表雄酮硫酸盐酯（DHEA-S）或与贝那唑（BNZ）联合治疗（在巴西推荐用于治疗克氏锥虫感染）在两种不同克氏锥虫株的急性阶段是否有效：I 型（Y 株）和 II 型（玻利维亚株）的克氏锥虫。与未治疗的相比，单独使用 DHEA-S 或 BNZ 或联合使用均可显著降低 Y 株寄生虫载量。此外，DHEA-S 治疗可使玻利维亚株清除。DHEA-S 的这种保护作用与宿主的免疫反应有关，证据是干扰素-γ和白细胞介素-2水平升高。DHEA-S 治疗还增加了腹腔巨噬细胞水平和亚硝酸盐的产生。与单独使用 BNZ 或联合使用 DHEA-S+BNZ 治疗克氏锥虫玻利维亚株感染动物相比，DHEA-S 治疗可有效降低死亡率。这些发现表明，激素治疗可能对治疗克氏锥虫感染具有保护作用。
