Mejias Maria Pilar, Fernandez-Brando Romina Jimena, Ramos Maria Victoria, Abrey-Recalde Maria Jimena, Zotta Elsa, Meiss Roberto, Palermo Marina Sandra
Instituto de Medicina Experimental (IMEX) (CONICET), Academia Nacional de Medicina, Pacheco de Melo 3081 (C1425AUM), Buenos Aires, Argentina.
Curr Pharm Des. 2016;22(34):5294-5299. doi: 10.2174/1381612822666160628080350.
Hemolytic Uremic Syndrome (HUS) caused by infections with Shiga toxin (Stx)-producing E. coli is a life-threatening complication characterized by acute renal failure, thrombocytopenia and hemolytic anemia. Stx is the main pathogenic factor. Therefore, the mouse model by intravenous administration of a single lethal dose of Stx is often used to explore its pathogenic mechanisms.
The aim of this work was to develop an alternative mouse model of Stx type 2 (Stx2) intoxication to evaluate new therapeutic strategies.
One lethal dose of Stx2 was divided in four daily doses. We observed a dose-dependent toxicity characterized by neutrophilia, leukocytopenia and renal damage. Most importantly, we demonstrated that the polyclonal anti-Stx2 serum was able to protect mice from fatal evolution even when administered together the third dose of Stx2.
This model would provide an advantage for evaluation of therapeutic strategies. Furthermore, the results presented herein suggest that appropriate treatment with anti-Stx2 agents following the appearance of initial clinical signs may block the ongoing outcome or may alleviate disease in patients who have just been diagnosed with HUS. However, the delay in the onset of therapy would be unsafe.
由产志贺毒素（Stx）的大肠杆菌感染引起的溶血尿毒综合征（HUS）是一种危及生命的并发症，其特征为急性肾衰竭、血小板减少和溶血性贫血。Stx是主要致病因素。因此，静脉注射单一致死剂量Stx的小鼠模型常被用于探究其致病机制。
本研究旨在开发一种替代的2型Stx（Stx2）中毒小鼠模型，以评估新的治疗策略。
将单一致死剂量的Stx2分为四个每日剂量。我们观察到了以中性粒细胞增多、白细胞减少和肾损伤为特征的剂量依赖性毒性。最重要的是，我们证明即使在给予第三剂Stx2时同时注射，多克隆抗Stx2血清也能够保护小鼠免于致命结局。
该模型将为评估治疗策略提供优势。此外，本文结果表明，在出现初始临床症状后用抗Stx2药物进行适当治疗，可能会阻断疾病的进展或减轻刚被诊断为HUS患者的病情。然而，治疗开始的延迟将是不安全的。
