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首页> 外文期刊>Infection and immunity >Inhibition of lipopolysaccharide-associated endotoxin activities in vitro and in vivo by the human anti-lipid A monoclonal antibody SdJ5-1.17.15.
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Inhibition of lipopolysaccharide-associated endotoxin activities in vitro and in vivo by the human anti-lipid A monoclonal antibody SdJ5-1.17.15.

机译：人抗脂质A单克隆抗体SdJ5-1.17.15在体外和体内抑制脂多糖相关的内毒素活性。

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摘要

The present study evaluated the effect of a novel anti-lipid A monoclonal antibody, termed SdJ5, on the in vitro production of tumor necrosis factor alpha (TNF-alpha) and interleukin-1 beta by endotoxin- or lipopolysaccharide (LPS)-challenged human peripheral blood mononuclear cells (hPBMC). In addition, the present study determined whether SdJ5 could neutralize the in vivo toxicity of LPS. SdJ5, at a concentration equal to or greater than 3 micrograms/ml, specifically inhibited TNF-alpha and interleukin-1 beta production by hPBMC stimulated with every type of LPS and lipid A assessed. SdJ5 also showed a significantly greater inhibition of cytokine production than a nonrelevant human immunoglobulin M myeloma control. The SdJ5-mediated inhibition of TNF-alpha production was rapid, as the simultaneous addition of the SdJ5 and LPS still resulted in a marked decrease in hPBMC cytokine synthesis. The ability of SdJ5 to neutralize in vivo toxicity was also determined by using LPS from four different strains of gram-negative bacteria. LPS, when preincubated with SdJ5, resulted in a significant decrease in the 24-h mortality rate compared with that for the control. These studies show that the anti-lipid A monoclonal antibody SdJ5 can modulate LPS-induced cytokine production in vitro and increase the survival rate of rats challenged with lethal doses of LPS.
机译：本研究评估了新型抗脂质A单克隆抗体SdJ5对内毒素或脂多糖（LPS）攻击的人体外产生肿瘤坏死因子α（TNF-alpha）和白介素1β的影响外周血单个核细胞（hPBMC）。此外，本研究确定了SdJ5是否可以中和LPS的体内毒性。浓度等于或大于3微克/毫升的SdJ5通过抑制每种类型的LPS和脂质A刺激的hPBMC特异性抑制TNF-α和白介素-1β的产生。与不相关的人免疫球蛋白M骨髓瘤对照相比，SdJ5还显示出对细胞因子产生的抑制作用明显更大。 SdJ5介导的TNF-α产生的抑制作用很快，因为同时添加SdJ5和LPS仍然导致hPBMC细胞因子合成显着下降。还通过使用来自四种不同革兰氏阴性菌菌株的LPS来测定SdJ5中和体内毒性的能力。当与SdJ5预孵育时，LPS与对照组相比，导致24小时死亡率显着降低。这些研究表明，抗脂质A单克隆抗体SdJ5可以在体外调节LPS诱导的细胞因子产生，并提高用致死剂量LPS​​攻击的大鼠的存活率。

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