Morrison D C
Department of Microbiology, Molecular Genetics and Immunology University of Kansas Medical Center, Kansas City 66160, USA.
Prog Clin Biol Res. 1998;397:199-207.
Since the earliest days of antibiotic chemotherapy to treat infection with Gram-negative microbes, investigators have recognized that such treatments may result in the release of microbial constituents that might, in turn, exacerbate the pathophysiological manifestations of disease. Both in vitro studies and in vivo animal experiments have over the years provided evidence in support of this concept; however, the actual clinical importance of this phenomenon to patients with Gram-negative sepsis is unclear. Recently published reports from a number of laboratories have shown that cell wall-active antibiotics that differ in their fundamental mechanisms of action in disrupting microbial growth (via selective interactions with various penicillin binding proteins) also differ in their relative ability to induce the release of biologically active endotoxin both in vitro and in vivo. Further, quantitative differences in total endotoxin release correlate well with antibiotic-initiated morphological changes in the microbe. Of potential significance is the finding that these differences are also reflected in differential production of cytokines from endotoxin-stimulated mononuclear phagocytes and other host target cells, including 11-6 and TNF. Since these immunologic hormones have been strongly implicated as contributing factors to the pathogenesis of Gram-negative sepsis, interest in the potential use of this chemotherapeutic approach as a means of controlling the host immunopathologic response has increased. Carefully controlled clinical trials in which different antibiotic treatments are correlated with production of cytokines will be of significant potential value in evaluating the actual significance of this phenomenon in the Gram-negative septic patient.
自最早使用抗生素化疗来治疗革兰氏阴性菌感染以来，研究人员就已认识到，此类治疗可能会导致微生物成分的释放，进而可能会加剧疾病的病理生理表现。多年来，体外研究和体内动物实验均提供了支持这一概念的证据；然而，这一现象对革兰氏阴性菌败血症患者的实际临床重要性尚不清楚。一些实验室最近发表的报告表明，细胞壁活性抗生素在破坏微生物生长的基本作用机制（通过与各种青霉素结合蛋白的选择性相互作用）方面存在差异，它们在体外和体内诱导生物活性内毒素释放的相对能力也有所不同。此外，总内毒素释放的定量差异与抗生素引发的微生物形态变化密切相关。具有潜在意义的是，这些差异也反映在内毒素刺激的单核吞噬细胞和其他宿主靶细胞（包括IL-6和TNF）产生细胞因子的差异上。由于这些免疫激素被强烈认为是革兰氏阴性菌败血症发病机制的促成因素，因此人们对将这种化疗方法作为控制宿主免疫病理反应手段加以潜在应用的兴趣有所增加。在不同抗生素治疗与细胞因子产生相关的严格对照临床试验，对于评估这一现象在革兰氏阴性菌败血症患者中的实际重要性具有重大潜在价值。
