Donia Marco, Mangano Katia, Amoroso Alfredo, Mazzarino Maria Clorinda, Imbesi Rosa, Castrogiovanni Paola, Coco Marinella, Meroni Pierluigi, Nicoletti Ferdinando
Department of Biomedical Sciences, School of Medicine, University of Catania, Catania, Italy.
J Autoimmun. 2009 Sep;33(2):135-40. doi: 10.1016/j.jaut.2009.06.003. Epub 2009 Jul 21.
We have presently evaluated the effects of the immunomodulatory drug rapamycin on the course of protracted relapsing experimental allergic encephalomyelitis (PR-EAE) in Dark Agouti (DA) rats, which serves as a preclinical model of multiple sclerosis. The data show that the oral administration of rapamycin at 3 mg/kg for 28 consecutive days significantly ameliorated the course of PR-EAE in DA rats. The rats that received the medication had significantly lower clinical cumulative scores and shorter duration of the disease than did the control rats treated with the vehicle. The milder course of the disease was associated with a reduction of the histopathological signs associated to EAE: increased percentage of splenic CD4+CD25 + Foxp3+ Tregs and concomitant reduction of splenic CD8+T cells. These data suggest that rapamycin has pharmacological potential worthy of consideration in the treatment of MS patients.
我们目前评估了免疫调节药物雷帕霉素对黑褐大鼠（DA大鼠）慢性复发性实验性自身免疫性脑脊髓炎（PR-EAE）病程的影响，DA大鼠可作为多发性硬化症的临床前模型。数据显示，连续28天口服3mg/kg雷帕霉素可显著改善DA大鼠的PR-EAE病程。接受药物治疗的大鼠临床累积评分显著低于接受赋形剂治疗的对照大鼠，且疾病持续时间更短。病情较轻与EAE相关的组织病理学体征减轻有关：脾脏CD4+CD25 + Foxp3+调节性T细胞百分比增加，同时脾脏CD8+T细胞减少。这些数据表明，雷帕霉素在治疗MS患者方面具有值得考虑的药理学潜力。
