A comparison of the immunomodulating properties of two forms of monophosphoryl lipid A analogues.

A G Johnson, M A Tomai, Y F Chen, M Odean
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引用次数: 16

Abstract

This investigation compared the immunomodulating activities of two forms monophosphoryl lipid A, which are analogues of bacterial lipopolysaccharides with little or no toxicity. Tested were a synthetic compound designated 504 and a purified compound, isolated from bacterial cell walls designated MPL. Both of these clinical adjuvant candidates were effective in mice in exerting strong immunomodulating activity in the following areas: (a) enhancing antibody production in young and aging mice; (b) suppressing antibody formation under different experimental conditions; (c) activating macrophages to secrete interleukin 1, hydrogen peroxide, and superoxide anion; and (d) stimulating proliferation of spleen cells from C3H/HeN mice. Both exhibited considerably reduced toxicity in LD50 assays when compared to native lipopolysaccharides (LPS). The LD50 for MPL was 225 times and that of compound 504, 40 times that of native LPS in the exquisitely sensitive, galactosamine-loaded C57BL/6 murine strain.

两种形式的单磷酰脂质A类似物免疫调节特性的比较。
本研究比较了两种形式的单磷酰脂质A的免疫调节活性,它们是细菌脂多糖的类似物,毒性很小或没有毒性。测试了一种合成化合物504和一种从细菌细胞壁中分离出来的纯化化合物MPL。这两种临床佐剂候选物在小鼠中都有效,在以下方面发挥了强大的免疫调节活性:(a)增强年轻和老年小鼠的抗体产生;(b)不同实验条件下抑制抗体形成;(c)激活巨噬细胞分泌白细胞介素1、过氧化氢和超氧阴离子;(d)刺激C3H/HeN小鼠脾细胞增殖。与天然脂多糖(LPS)相比,两者在LD50测定中均表现出明显降低的毒性。在敏感的半乳糖胺负载C57BL/6小鼠菌株中,MPL的LD50是天然LPS的225倍,化合物504的LD50是天然LPS的40倍。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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