Godot Véronique, Harraga Saïd, Podoprigora Guennady, Liance Martine, Bardonnet Karine, Vuitton Dominique A
World Health Organization Collaborating Center on Prevention and Treatment of Human Echinococcosis, Faculté de Médecine et de Pharmacie et Centre Hospitalier Universitaire, Université de Franche-Comte, Besançon, France.
Gastroenterology. 2003 May;124(5):1441-50. doi: 10.1016/s0016-5085(03)00273-7.
BACKGROUND & AIMS: Hepatic alveolar echinococcosis (AE), caused by the larval growth of Echinococcus multilocularis, is one of the most lethal helminthic diseases with no satisfactory treatment. Advances in the understanding of the host's immune response (Th2 responses associated with a progressive form of AE), have driven the research towards immune stimulation as an alternative possibility to treat patients. We previously reported clinical stabilization associated with a shift from a Th2 to a Th1 cytokine profile in an AE patient treated with interferon (IFN)alpha.
The effects of recombinant IFN alpha-2a were analyzed in the susceptible C57BL/6J E. multilocularis infected mice. Parasitic burden, macrophage functions, and specific T-cell responses were studied 15, 45, and 90 days postinfection.
After 90 days postinfection, 75% of infected IFN alpha-2a-treated mice had no hepatic lesions and half were fully protected. IFN alpha-2a treatment markedly decreased the abnormally elevated production of IL-10 in both spleen cell cultures and peritoneal macrophage cultures from infected mice and restored phagocytosis and oxidative metabolism of macrophages. It also inhibited IL-6 and IL-13 antigen-induced secretions in spleen cell cultures.
Through its immunoregulatory properties, IFN alpha-2a may be effective in a helminthic liver infection and is a promising candidate for clinical application in AE.
肝泡型包虫病（AE）由多房棘球绦虫幼虫生长引起，是最致命的蠕虫病之一，尚无令人满意的治疗方法。对宿主免疫反应（与进展型AE相关的Th2反应）认识的进展推动了将免疫刺激作为治疗患者的一种替代可能性的研究。我们之前报道了一名接受干扰素（IFN）α治疗的AE患者出现了从Th2细胞因子谱向Th1细胞因子谱转变并伴有临床病情稳定的情况。
在易感的C57BL/6J多房棘球绦虫感染小鼠中分析重组IFNα-2a的作用。在感染后15、45和90天研究寄生虫负荷、巨噬细胞功能和特异性T细胞反应。
感染后90天，75%接受IFNα-2a治疗的感染小鼠没有肝脏病变，半数得到完全保护。IFNα-2a治疗显著降低了感染小鼠脾细胞培养物和腹腔巨噬细胞培养物中异常升高的IL-10产生，并恢复了巨噬细胞的吞噬作用和氧化代谢。它还抑制了脾细胞培养物中IL-6和IL-13抗原诱导的分泌。
通过其免疫调节特性，IFNα-2a可能对蠕虫性肝脏感染有效，是AE临床应用中有前景的候选药物。
