SDZ mrl953对活菌和热杀菌致小鼠死亡的保护作用。

Circulatory shock Pub Date : 1994-03-01
E Schütze, J Hildebrandt, E Liehl, C Lam
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引用次数: 0

摘要

研究了单糖脂质a类似物SDZ MRL 953对实验性脓毒性休克的保护作用,并对注射LPS和接种热杀菌或活菌进行了研究。雌性B6D2F1小鼠被半乳糖胺(800 mg/kg)加不同剂量的大肠杆菌、铜绿假单胞菌、鼠伤寒沙门菌和金黄色葡萄球菌热杀菌株或产马沙门菌LPS联合攻击。在一些实验中,亚致死接种的活菌分离株也与半乳糖胺联合使用。超过90%的动物在注射半乳糖胺的同时或腹腔注射半乳糖胺后4小时内死亡。当省略半乳糖胺或在微生物或LPS挑战后给予半乳糖胺时,未观察到死亡。用SDZ MRL 953 (1-10 mg/kg)预处理动物,使动物对细菌和LPS的致死效应具有时间和剂量依赖性。对照组小鼠的tnf - α水平在细菌或LPS攻击后2小时上升至大于600 pg/ml,但在SDZ MRL 953预处理的动物中低于检测水平。当小鼠抗tnf - α单克隆抗体被预防性给予时,对热杀细菌或LPS的感染和毒性也有保护作用。总之,这些数据表明,SDZ MRL 953增强了小鼠对热杀革兰氏阴性菌和金黄色葡萄球菌毒性的抗性,并减弱了宿主对活细菌的反应,这种反应可能导致不可逆的休克和死亡。
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Protection of mice from mortality caused by living and heat-killed bacteria by SDZ MRL 953.

Protective effects of SDZ MRL 953, a monosaccharidic lipid A analog with a reduced toxicity, were investigated in models of experimental septic shock caused by injections of LPS, and inoculations of heat-killed or live bacteria. Female B6D2F1 mice were challenged with a combination of galactosamine (800 mg/kg) plus various doses of heat-killed isolates of Escherichia coli, Pseudomonas aeruginosa, Salmonella typhimurium, and Staphylococcus aureus or LPS from Salmonella abortus equi. In some experiments, isolates of living bacteria at sublethal inocula were also combined with galactosamine. More than 90% of the animals died within 24 hr when the challenge was performed either simultaneously with or up to 4 hr after an intraperitoneal administration of galactosamine. No death was observed when galactosamine was omitted or administered after the microbial or LPS challenge. Pretreatment of the animals with SDZ MRL 953 (1-10 mg/kg) rendered the animals resistant to the lethal effects of both bacterial and LPS challenge in a time- and dose-dependent manner. The levels of TNF-alpha in control mice rose to greater than 600 pg/ml 2 hr postbacterial or LPS challenge, but were below detection in animals pretreated with SDZ MRL 953. Protection against both the infection and the toxicity of heat-killed bacteria or LPS was also achieved when murine anti-TNF-alpha monoclonal antibody was administered prophylactically. Together, these data suggest that SDZ MRL 953 enhances the resistance of mice against the toxicity of heat-killed gram-negative bacteria and S. aureus, and attenuates host responses to living bacteria which may lead to irreversible shock and death.

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Comparison of binding specificity and the function of two human IgM anti-lipid A monoclonal antibodies. Hypertonic saline/dextran versus lactated Ringer's treatment for hemorrhage in dehydrated swine. Lysozyme regulates LPS-induced interleukin-6 release in mice. Liver oxygen uptake dependence and mitochondrial function in septic rats. Efficacy of continuous arteriovenous hemofiltration in endotoxic shock.
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