Grandel Ulrich, Grimminger Friedrich
Department of Internal Medicine, Justus-Liebig-University, 35392 Giessen, Germany.
Crit Rev Immunol. 2003;23(4):267-99. doi: 10.1615/critrevimmunol.v23.i4.20.
The virulence of pathogenic bacteria is critically dependent on their ability to produce toxins that attack eukaryotic target cells. Microbial toxins are either structural components of the bacterial cell wall (endotoxins) or actively secreted proteins (exotoxins). Sepsis and septic shock, which represent major causes of mortality in modern intensive care medicine, are caused by an inadequate inflammatory and immunological host response to bacterial infection. Emerging evidence suggests that the systemic spread of microbial toxins, rather than bacteremia itself, is the crucial event in the pathogenesis of this dramatic dysregulation. The endothelium, with its diversity of physiological functions is a main target of bacterial toxins. The resulting endothelial dysfunction is believed to contribute to the underlying pathomechanisms and the collapse of homeostasis of organ function. In vitro, bacterial toxins induce subtle alterations of endothelial cell function rather than massive cell damage. Furthermore, bacterial toxins targeting endothelial cells severely alter the behavior of extravascular cells and circulating leukocytes via excessive formation of vasoactive mediators and overexpression of adhesion molecules. Research on the effects of microbial toxins on vascular endothelium has broadened our general understanding of microbial strategies to induce organ damage, even in the absence of viable bacteria. Combining antitoxin strategies with antibiotic therapy may prove to be of benefit to patients suffering from bacterial sepsis in the future.
病原菌的毒力严重依赖于其产生攻击真核靶细胞毒素的能力。微生物毒素要么是细菌细胞壁的结构成分（内毒素），要么是主动分泌的蛋白质（外毒素）。脓毒症和脓毒性休克是现代重症医学中主要的死亡原因，它们是由宿主对细菌感染的炎症和免疫反应不足引起的。新出现的证据表明，微生物毒素的全身扩散而非菌血症本身，是这种严重失调发病机制中的关键事件。具有多种生理功能的内皮是细菌毒素的主要靶标。由此产生的内皮功能障碍被认为是潜在病理机制以及器官功能稳态崩溃的原因。在体外，细菌毒素引起内皮细胞功能的细微改变而非大量细胞损伤。此外，靶向内皮细胞的细菌毒素通过过度形成血管活性介质和过度表达黏附分子，严重改变血管外细胞和循环白细胞的行为。对微生物毒素对血管内皮影响的研究拓宽了我们对微生物诱导器官损伤策略的总体认识，即使在没有活菌的情况下也是如此。将抗毒素策略与抗生素治疗相结合可能在未来被证明对患有细菌性脓毒症的患者有益。
