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首页> 美国卫生研究院文献>Infection and Immunity >Stimulation of nonspecific resistance to infection induced by muramyl dipeptide analogs substituted in the gamma-carboxyl group and evaluation of N alpha-muramyl dipeptide-N epsilon-stearoyllysine.
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Stimulation of nonspecific resistance to infection induced by muramyl dipeptide analogs substituted in the gamma-carboxyl group and evaluation of N alpha-muramyl dipeptide-N epsilon-stearoyllysine.

机译：刺激由被γ-羧基取代的多聚二甲苯基二肽类似物诱导的对感染的非特异性抗性并评估Nα-村基二肽-Nε-硬脂酰赖氨酸。

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摘要

Stimulation of resistance to infection induced by the analogs of muramyl dipeptide (MDP) having substituted functions in the gamma-carboxyl group of D-isoglutamyl residue was examined in experimental Escherichia coli infections in mice. An MDP analog which is an efficient strengthener of resistance to infection, N alpha-MDP-N epsilon-stearoyllysine [MDP-Lys(L18)], was selected through the comparative assessment of a number of compounds in three categories: (i) gamma-alkylamides, (ii) gamma-esters, and (iii) N alpha-MDP-N epsilon-acyllysine derivatives. Furthermore, the antiinfectious activity of MDP-Lys(L18) was evaluated bacteriologically in comparison with that of MDP. The effect of MDP-Lys(L18) on the susceptibility of mice to infections with various species of microorganisms was studied. Protective activity was greatest against E. coli and staphylococcal infections, considerable against Pseudomonas and Candida infections, and least against Klebsiella infection. The effects of bacterial inoculum size and MDP treatment timing, dose, and route of administration on protective activity were studied. The efficacy of MDP-Lys(L18) in protection tests was demonstrated for all administration routes, even the oral. Its high potency was confirmed by the smaller influence of inoculum size and particularly small value of the minimum dosage required for inducing protective activity. A decrease in bacterial survival was observed in the blood and organs of mice treated with the analog and infected with E. coli. The following two useful effects were obtained: the synergistic effect of glycopeptide and chemotherapeutic agents and the stimulation of resistance to infection in animals immunocompromised by cyclophosphamide treatment.
机译：在小鼠的实验性大肠杆菌感染中，检查了由在D-异谷氨酰基残基的γ-羧基上具有取代功能的Mulramyl二肽（MDP）类似物诱导的对感染的抗性刺激。通过对以下三类化合物的比较评估，选择了一种可以有效增强抗感染性的MDP类似物Nα-MDP-Nε-硬脂酰赖氨酸[MDP-Lys（L18）]。 -烷基酰胺，（ii）γ-酯和（iii）Nα-MDP-Nε-酰基赖氨酸衍生物。此外，与MDP相比，通过细菌学评估了MDP-Lys（L18）的抗感染活性。研究了MDP-Lys（L18）对小鼠感染各种微生物的敏感性的影响。对大肠杆菌和葡萄球菌感染的保护作用最大，对假单胞菌和念珠菌感染的保护作用最大，对克雷伯菌的保护作用最小。研究了细菌接种量和MDP处理时间，剂量和给药途径对保护活性的影响。证明了MDP-Lys（L18）在所有测试途径（包括口服）中的保护作用。接种物的影响较小，特别是诱导保护活性所需的最小剂量值较小时，证实了其高效力。在用类似物处理并感染了大肠杆菌的小鼠的血液和器官中观察到细菌存活率降低。获得了以下两个有用的效果：糖肽和化学治疗剂的协同作用以及在环磷酰胺治疗免疫受损的动物中刺激对感染的抵抗力。

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