Calandra T, Baumgartner J D, Glauser M P
Department of Internal Medicine, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
Prog Clin Biol Res. 1991;367:141-59.
Endotoxin is composed of lipid A, the toxic moiety, of the core region, a conserved structure among Gram-negative bacteria, and of the O-side chains, a highly variable part responsible for the antigenic specificity. The concept of cross-protection afforded by antiserum raised against the core region of endotoxin is supported by the following data: experimentally antiserum protected against infections caused by a wide range of Gram-negative bacteria or endotoxins; in patients with Gram-negative bacteremia, survival was associated with high levels of anti-core antibodies, and mortality was reduced by the prophylactic or therapeutic use of immune serum or plasma. However, the proof that protection is afforded by cross-protective anti-core antibodies is still lacking. Furthermore, many experimental studies and clinical studies trials have shown controversial results. Ongoing experimental studies and recently completed clinical trials, using either polyclonal or monoclonal anti-core antibodies should help clarify the issues both of the clinical efficacy and of the mechanism of protection. Tumor necrosis factor/cachectin has been unequivocally shown, both in experimental animal models and in humans to be a pivotal mediator of the clinical and humoral manifestations of shock induced by endotoxin or by whole Gram-negative bacteria. In humans, TNF was been transiently detected in the blood of volunteers challenged with endotoxin, in a small proportion of patients with Gram-negative sepsis, but in the vast majority of patients with established septic shock. However, in patients the magnitude and the evolution of the blood concentration of TNF differed from that observed in animal models or in human volunteers after an acute challenge with either Gram-negative bacteria or endotoxin, probably reflecting differences in infectious stimuli. In children with meningococemia and in adults with Gram-negative septic shock, TNF was associated with the patient's outcome. Anti-TNF monoclonal antibodies are presently undergoing clinical investigation in patients with septic shock. However, one should keep in mind that TNF serves both beneficial and detrimental functions depending upon its concentration in body fluids.
内毒素由脂质A（毒性部分）、核心区域（革兰氏阴性菌中的保守结构）以及O侧链（负责抗原特异性的高度可变部分）组成。针对内毒素核心区域产生的抗血清所提供的交叉保护概念得到了以下数据的支持：实验表明，抗血清可保护机体免受多种革兰氏阴性菌或内毒素引起的感染；在革兰氏阴性菌血症患者中，生存与高水平的抗核心抗体相关，免疫血清或血浆的预防性或治疗性使用可降低死亡率。然而，仍缺乏交叉保护性抗核心抗体提供保护的证据。此外，许多实验研究和临床试验结果存在争议。正在进行的实验研究以及最近完成的使用多克隆或单克隆抗核心抗体的临床试验，应有助于阐明临床疗效和保护机制等问题。在实验动物模型和人类中均已明确表明，肿瘤坏死因子/恶病质素是内毒素或全革兰氏阴性菌诱导的休克的临床和体液表现的关键介质。在人类中，在内毒素激发的志愿者血液中、一小部分革兰氏阴性菌败血症患者中，但在绝大多数已发生感染性休克的患者中，均可短暂检测到肿瘤坏死因子。然而，患者血液中肿瘤坏死因子浓度的幅度和变化与革兰氏阴性菌或内毒素急性激发后在动物模型或人类志愿者中观察到的情况不同，这可能反映了感染刺激的差异。在患有脑膜炎球菌血症的儿童和患有革兰氏阴性菌感染性休克的成人中，肿瘤坏死因子与患者的预后相关。抗肿瘤坏死因子单克隆抗体目前正在感染性休克患者中进行临床研究。然而，应牢记肿瘤坏死因子根据其在体液中的浓度发挥有益和有害的功能。
