Inada K, Endo S, Yamashita H, Suzuki M, Yoshida H, Yoshida M
Department of Bacetriology, Iwate Medical University.
Kansenshogaku Zasshi. 1993 Nov;67(11):1108-14. doi: 10.11150/kansenshogakuzasshi1970.67.1108.
Mouse anti-endotoxin monoclonal antibody (E5) is now under clinical trial (Phase II) in Japan by assessing clinical findings and plasma endotoxin levels. We attempted to evaluate an inhibitory effect of E5 on hypotension induced by endotoxin and TNF-alpha. Systolic blood pressure was measured with a programmable sphygmomanometer using the tail-cuff method. The mixture of endotoxin (E. coli O111:B4, Sigma, 2 micrograms/mouse) and recombinant mouse TNF-alpha (Genzyme, 8000 units) were injected into mice (ddY, 6-8-weeks-olds), and the change of blood pressure was observed for 3 hrs. The mixture significantly decreased the blood pressure to about 70% of the control. E5 (20 micrograms/mouse), which was injected 10 min before, significantly abrogated the effect of endotoxin and TNF-alpha. The hypotension induced by the mixture was definitely inhibited by the injection of E5 (50, 100 micrograms/mouse), injected 10 min later, or the injection of E5 (100 micrograms/mouse) 30 min later. We previously found that E5 prevents the lethality induced by a concomitant injection of endotoxin, TNF-alpha and IL-2. These results suggest that E5 effective for inhibition of endotoxin activity in vivo.
小鼠抗内毒素单克隆抗体（E5）目前正在日本进行临床试验（II期），通过评估临床症状和血浆内毒素水平来开展。我们试图评估E5对内毒素和肿瘤坏死因子-α（TNF-α）诱导的低血压的抑制作用。使用尾套法，通过可编程血压计测量收缩压。将内毒素（大肠杆菌O111:B4，西格玛公司，2微克/只小鼠）和重组小鼠TNF-α（基因重组公司，8000单位）的混合物注射到小鼠（ddY品系，6至8周龄）体内，并观察3小时内血压的变化。该混合物可使血压显著降低至对照组的约70%。提前10分钟注射的E5（20微克/只小鼠）可显著消除内毒素和TNF-α的作用。提前10分钟注射的E5（50、100微克/只小鼠）或30分钟后注射的E5（100微克/只小鼠）可明确抑制该混合物诱导的低血压。我们之前发现E5可预防同时注射内毒素、TNF-α和白细胞介素-2所诱导的致死性。这些结果表明E5在体内对抑制内毒素活性有效。
