Mehra I V, Gottlieb J E, Nash D B
Department of Pharmacy, Jefferson Medical College, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania.
Pharmacotherapy. 1993 Mar-Apr;13(2):128-34.
Gram-negative sepsis is a common event in hospitalized patients and is a leading cause of death in the United States. Endotoxin (lipopolysaccharide, LPS), a component of the cell wall of gram-negative microorganisms, is responsible for the cascade of events leading to the sepsis syndrome consisting of fever, tachycardia, tachypnea, and evidence of organ hypoperfusion. The lipid A region of endotoxin produces most of these biologic and toxic effects. Monoclonal IgM antibodies directed against the lipid A portion of endotoxin (anti-LPS MoAb) have been developed for the treatment of gram-negative sepsis. Results of two large-scale clinical trials suggest that these antibodies offer clinically and statistically significant reductions in mortality by a factor of about one-third. However, in both trials, this apparent beneficial effect was limited to particular subsets of patients, and no overall benefit was seen. These considerations, in addition to the likely high cost of the agents, pose questions about their ultimate use in the treatment of patients with gram-negative sepsis. Nevertheless, the logic of the approach, the demonstration of efficacy in disease models, and the advances in modern techniques of molecular biology all suggest that these or other closely related products will play a significant role in the treatment of this disorder.
革兰氏阴性菌败血症在住院患者中很常见，是美国主要的死亡原因之一。内毒素（脂多糖，LPS）是革兰氏阴性微生物细胞壁的一种成分，是导致败血症综合征一系列事件的罪魁祸首，败血症综合征包括发热、心动过速、呼吸急促以及器官灌注不足的迹象。内毒素的脂质A区域产生了这些大部分的生物学和毒性作用。针对内毒素脂质A部分的单克隆IgM抗体（抗LPS单克隆抗体）已被开发用于治疗革兰氏阴性菌败血症。两项大规模临床试验的结果表明，这些抗体可使死亡率在临床和统计学上显著降低约三分之一。然而，在这两项试验中，这种明显的有益效果仅限于特定的患者亚组，并未观察到总体益处。除了这些药物可能成本高昂之外，这些因素也引发了关于它们在治疗革兰氏阴性菌败血症患者中最终用途的疑问。尽管如此，该方法的合理性、在疾病模型中疗效的证明以及现代分子生物学技术的进步都表明，这些或其他密切相关的产品将在这种疾病的治疗中发挥重要作用。
