Department of Immunology, Erasmus MC University Medical Center, Rotterdam, the Netherlands.
Clin Exp Immunol. 2010 Jun;160(3):466-78. doi: 10.1111/j.1365-2249.2010.04112.x. Epub 2010 Mar 16.
The marked improvement of several immune-mediated inflammatory diseases during pregnancy has drawn attention to pregnancy hormones as potential therapeutics for such disorders. Low molecular weight fractions derived from the pregnancy hormone human chorionic gonadotrophin (hCG) have remarkable potent immunosuppressive effects in mouse models of diabetes and septic shock. Based on these data we have designed a set of oligopeptides related to the primary structure of hCG and tested these in models of septic shock in mice and rhesus monkeys. We demonstrate that mice exposed to lipopolysaccharide (LPS) and treated subsequently with selected tri-, tetra-, penta- and hepta-meric oligopeptides (i.e. MTR, VVC, MTRV, LQGV, AQGV, VLPALP, VLPALPQ) are protected against fatal LPS-induced septic shock. Moreover, administration of a cocktail of three selected oligopeptides (LQGV, AQGV and VLPALP) improved the pathological features markedly and nearly improved haemodynamic parameters associated with intravenous Escherichia coli-induced septic shock in rhesus monkeys. These data indicate that the designed hCG-related oligopeptides may present a potential treatment for the initial hyperdynamic phase of septic shock in humans.
妊娠期间几种免疫介导的炎症性疾病的显著改善引起了人们对妊娠激素作为此类疾病潜在治疗方法的关注。来自妊娠激素人绒毛膜促性腺激素（hCG）的低分子量部分在糖尿病和败血症性休克的小鼠模型中具有显著的强效免疫抑制作用。基于这些数据，我们设计了一组与 hCG 一级结构相关的寡肽，并在小鼠和恒河猴的败血症休克模型中对这些寡肽进行了测试。我们证明，暴露于脂多糖（LPS）并随后用选定的三、四、五和七聚体寡肽（即 MTR、VVC、MTRV、LQGV、AQGV、VLPALP、VLPALPQ）处理的小鼠可以预防致命的 LPS 诱导的败血症性休克。此外，给予三种选定的寡肽（LQGV、AQGV 和 VLPALP）的混合物可显著改善病理特征，并几乎改善与静脉内大肠杆菌诱导的败血症性休克相关的血流动力学参数在恒河猴中。这些数据表明，设计的 hCG 相关寡肽可能为人类败血症性休克初始高动力期提供一种潜在的治疗方法。
