Treatment of toxic shock syndrome with endotoxin-neutralizing antibody.
Treatment of toxic shock syndrome with endotoxin-neutralizing antibody.
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用内毒素中和抗体治疗中毒性休克综合征。
DOI：
10.1016/0022-4804(89)90014-0
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发表时间：
1989
期刊：
影响因子：
--
通讯作者：
Dunn,DL
中科院分区：
文献类型：
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作者：
Priest,BP;Schlievert,PM;Dunn,DL
中毒性休克综合征毒素-1 （TSST-1）增强宿主对内毒素（脂多糖，LPS）的敏感性是中毒性休克综合征发病的重要机制。在这些研究中，我们试图确定内毒素中和单克隆抗体是否可用于治疗中毒性休克综合征。我们分离了一株小鼠单克隆杂交瘤（3-H3），该杂交瘤分泌特异性大肠杆菌0111:B4 LPS的单克隆抗体（mAb）。脾细胞共培养。coli0111:B4 LPS显示，在3-H3单抗存在下，有丝分裂活性降低高达60%，而对照单抗不存在，表明该抗体在体外中和内毒素。用3-H3单抗或对照单抗预处理的家兔皮下注射the。coli0111: B4有限合伙人。一天后，兔子收到了de。coli0111:B4 LPS诱导皮肤史瓦兹曼反应。与对照组（5/6）相比，用3-H3单抗预处理的家兔没有发生这种反应（0/6），表明该抗体在体内中和内毒素（P< 0.05）。当该抗体在致死性中毒性休克综合征兔模型中进行评估时，经抗体预处理的家兔在TSST-1 andE攻毒后的存活率（8/14）高于生理盐水对照组（1/10）。coli0111:B4 LPS （P< 0.05）。由于怀疑低水平的内源性LPS可能在临床中毒性休克综合征期间增强TSST-1活性，我们假设内毒素中和抗体可能在治疗这种致命疾病过程中有用。
The enhancement of host susceptibility to endotoxin (lipopolysaccharide, LPS) by toxic shock syndrome toxin-1 (TSST-1) is an important mechanism in the pathogenesis of toxic shock syndrome. In these studies, we sought to determine whether an endotoxin-neutralizing monoclonal antibody could be useful in the treatment of toxic shock syndrome. We isolated a murine monoclonal hybridoma (3-H3) which secreted monoclonal antibody (mAb) specific forEscherichia coli0111:B4 LPS. Spleen cells cocultured withE. coli0111:B4 LPS demonstrated up to a 60% decrease in mitogenic activity in the presence of 3-H3 mAb, but not control mAb, demonstrating that this antibody neutralized endotoxinin vitro. Rabbits pretreated with 3-H3 mAb or control mAb were injected intradermally withE. coli0111:B4 LPS. One day later rabbits receivedE. coli0111:B4 LPS intravenously to elicit the dermal Shwartzman reaction. Rabbits pretreated with 3-H3 mAb did not develop this reaction (0/6) compared to animals pretreated with control mAb (5/6), demonstrating that this antibody neutralized endotoxinin vivo(P< 0.05). When this antibody was evaluated in a rabbit model of lethal toxic shock syndrome, rabbits pretreated with antibody demonstrated greater survival (8/14) than saline control animals (1/10) after challenge with TSST-1 andE. coli0111:B4 LPS (P< 0.05). Since the suspicion exists that low levels of endogenous LPS may potentiate TSST-1 activity during clinical toxic shock syndrome, we hypothesized that endotoxin-neutralizing antibodies could be useful in the treatment of this lethal disease process.