Andrä Jörg, Gutsmann Thomas, Garidel Patrick, Brandenburg Klaus
Forschungszentrum Borstel, Biophysics Division, Leibniz-Zentrum für Medizin und Biowissenschaften, Borstel, Germany.
J Endotoxin Res. 2006;12(5):261-77. doi: 10.1179/096805106X118852.
A basic challenge in the treatment of septic patients in critical care units is the release of bacterial pathogenicity factors such as lipopolysaccharide (LPS, endotoxin) from the cell envelope of Gram-negative bacteria due to killing by antibiotics. LPS aggregates may interact with serum and membrane proteins such as LBP (lipopolysaccharide-binding protein) and CD14 leading to the observed strong reaction of the immune system. Thus, an effective treatment of patients infected by Gram-negative bacteria must comprise beside bacterial killing the neutralization of endotoxins. Here, data are summarized for synthetic compounds indicating the stepwise development to very effective LPS-neutralizing agents. These data include synthetic peptides, based on the endotoxin-binding domains of natural binding proteins such as lactoferrin, Limulus anti-LPS factor, NK-lysin, and cathelicidins or based on LPS sequestering polyamines. Many of these compounds could be shown to act not only in vitro, but also in vivo (e.g. in animal models of sepsis), and might be useful in future clinical trials and in sepsis therapy.
在重症监护病房治疗脓毒症患者面临的一个基本挑战是，革兰氏阴性菌的细胞壁因抗生素杀菌作用而释放出细菌致病因子，如脂多糖（LPS，内毒素）。LPS聚集体可能与血清和膜蛋白如LBP（脂多糖结合蛋白）和CD14相互作用，导致观察到的免疫系统强烈反应。因此，有效治疗革兰氏阴性菌感染的患者除了杀灭细菌外，还必须中和内毒素。在此，总结了合成化合物的数据，这些数据表明了向非常有效的LPS中和剂逐步发展的过程。这些数据包括基于天然结合蛋白（如乳铁蛋白、鲎抗LPS因子、NK-溶素和cathelicidins）的内毒素结合域或基于LPS螯合多胺的合成肽。这些化合物中的许多不仅在体外有作用，而且在体内（如脓毒症动物模型）也有作用，可能在未来的临床试验和脓毒症治疗中有用。
