Preincubation of endotoxin with monoclonal anti-lipid A (E5), but not in vivo treatment, inhibits circulatory dysfunction.
Preincubation of endotoxin with monoclonal anti-lipid A (E5), but not in vivo treatment, inhibits circulatory dysfunction.
复制标题
内毒素与单克隆抗脂质 A (E5) 预孵育（但不是体内处理）可抑制循环功能障碍。
DOI：
10.1097/00024382-199508000-00009
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发表时间：
1995
期刊：
影响因子：
--
通讯作者：
Schwartz,RW
中科院分区：
文献类型：
--
作者：
Arden,WA;Strodel,WE;Gross,DR;Anderson,KW;Oremus,R;Derbin,M;Schwartz,RW
针对毒性脂质的单抗(MAb)在体外已被证明能与脂类A结合，但临床试验结果喜忧参半。在53只接受大循环和提睾肌微循环测量的大鼠中，我们检测了E5，一种小鼠衍生的抗脂A单抗，在体外与LPS孵育时，或在给药前分别在体内给予时，是否能抑制内毒素诱导的循环功能障碍。与对照组(I组)相比，注射10 mg/kg大肠杆菌脂多糖(II组)的大鼠动脉压和心输出量显著降低，二、三、四级骨骼肌小动脉的红细胞运动速度明显减慢。在注射内毒素前90min注射E5 2 mg/kg(组III)并不能改善心血管功能。相反，输注前给予内毒素2 mg/kg(IV组)或10 mg/kg(V组)E5可显著减轻内毒素引起的大循环和微循环功能的改变。进一步研究抗脂A单抗的体外和体内中和能力之间的差异可能有助于解释这些制剂所取得的不同临床结果。
Monoclonal antibodies (mAb) directed against the toxic lipid A portion of lipopolysaccharide (LPS) have been shown to bind lipid A in vitro, but clinical trials of such mAbs have yielded mixed results. In 53 rats instrumented for macrocirculatory and cremaster muscle microcirculatory measurements, we examined whether E5, a murine-derived anti-lipid A mAb, could inhibit LPS-induced circulatory dysfunction when incubated with LPS in vitro or given separately in vivo prior to LPS administration. Compared with Control rats (Group I), rats infused with 10 mg/kg Escherichia coli LPS (Group II) displayed marked decreases in arterial pressure and cardiac output and marked decreases in erythrocyte velocity in second, third, and fourth order skeletal muscle arterioles. Infusion of 2 mg/kg E5 90 min prior to LPS infusion (Group III) did not improve cardiovascular performance. In contrast, incubation of LPS with either 2 mg/kg (Group IV) or 10 mg/kg (Group V) E5 prior to infusion significantly attenuated LPS-induced changes in both macrocirculatory and microcirculatory function. Further investigation of the disparity between the in vitro and in vivo neutralizing capacity of anti-lipid A mAbs may aid interpretation of the variable clinical results achieved with these preparations.