ANTIBODY IMMUNOTHERAPY OF GRAM-NEGATIVE BACTERIAL SEPSIS IN AN IMMUNOSUPPRESSED ANIMAL-MODEL
ANTIBODY IMMUNOTHERAPY OF GRAM-NEGATIVE BACTERIAL SEPSIS IN AN IMMUNOSUPPRESSED ANIMAL-MODEL
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DOI：
10.1097/00007890-198802000-00036
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发表时间：
1988-02-01
期刊：
影响因子：
6.2
通讯作者：
DUNN, DL
中科院分区：
文献类型：
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作者：
DUNN, DL
白细胞减少症、实体器官同种异体移植受者的免疫抑制是革兰氏阴性菌败血症的高风险，死亡率仍然高得令人无法接受（> 30%）。本研究的目的是确定针对脂多糖（LPS，内毒素）的鼠单克隆抗体 (MAb) 是否会降低免疫抑制小鼠因脓毒症损伤引起的致死率，并确定特定的抗体类别是否在这种情况下更有效。选择两种 MAb（3-H9 IgG3；7-B5、IgM），通过 ELISA、免疫点印迹和蛋白质印迹分析针对大肠杆菌 0111:B4 LPS 的 O 抗原多糖部分进行反应。静脉内施用 3-H9 MAb、7B-5 MAb 或无菌盐水。在大肠杆菌 0111-B4 细菌（静脉注射或腹腔注射加血红蛋白）或 LPS（静脉注射）攻击之前，对正常或中性粒细胞减少的 Swiss-Webster 小鼠进行试验。在正常小鼠中，静脉注射 3-H9 MAb 或 7-B5 MAb。在细菌或内毒素攻击之前立即导致 LD50 显着增加。在菌血症和腹膜炎模型中，中性粒细胞减少症使 LD50 降低近 1 log10。两种单克隆抗体都提供了类似的保护作用，将中性粒细胞减少小鼠的 LD50 提高了 log10。因此，接受任一单克隆抗体的中性粒细胞减少动物的死亡率与接受盐水的正常动物的死亡率几乎相同。在这三个模型中，这些单克隆抗体的保护能力没有显着差异。这些研究表明，针对 LPS 的单克隆抗体在正常或中性粒细胞减少动物的革兰氏阴性细菌败血症期间发挥保护作用。此外，所检查的特定 IgG 和 IgM MAb 提供了相似的保护能力。针对 LPS 的抗体可以提供一种附加的治疗形式，可以降低免疫抑制患者临床革兰氏阴性败血症期间的致死率。
Leukopenia, immunosuppressed recipients of solid organ allografts are at high risk for gram-negative bacteria sepsis, and mortality remains unacceptably high (> 30%). The purpose of this study was to determine whether murine monoclonal antibody (MAb) directed against lipopolysaccharide (LPS, endotoxin) would reduce lethality caused by a septic insult in immunosuppressed mice, and to determine if a specific antibody class would prove more efficacious in this setting. Two MAbs (3-H9 IgG3; 7-B5, IgM) were selected that reacted by ELISA, immunodot blot, and Western blot analysis against the O antigen polysaccharide portion of Escherichia coli 0111:B4 LPS. The 3-H9 MAb, 7B-5 MAb, or sterile saline was administered i.v. to normal or neutropenic Swiss-Webster mice immediately prior to an E. coli 0111-B4 bacterial (i.v. or i.p. plus hemoglobin) or LPS (i.v.) challenge. In normal mice, administration of 3-H9 MAb or 7-B5 MAb i.v. immediately prior to a bacterial or endotoxin challenge resulted in a significant increase in the LD50. Neutropenia lowered the LD50 by nearly one log10 in both the bacteremia and peritonitis models. Both MAbs provided similar protection, raising the LD50 one log10 in neutropenic mice. Thus neutropenic animals receiving either MAb had a mortality nearly identical to that of normal animals receiving saline. No significant difference between the protective capacity of these MAbs was noted in any of the three models. These studies demonstrate that MAbs directed against LPS exert protection during gram-negative bacterial sepsis in either normal or neutropenic animals. In addition, the particular IgG and IgM MAbs examined provided similar protective capacity. Antibody directed against LPS may provide an additive form of therapy that may serve to decrease lethality during clinical gram-negative sepsis in immunosuppressed patients.