Azuma I
Institute of Immunological Science, Hokkaido University, Sapporo, Japan.
Int J Immunopharmacol. 1992 Apr;14(3):487-96. doi: 10.1016/0192-0561(92)90180-s.
We have reported that the bacterial cell-wall skeletons, such as mycobacteria, nocardia, corynebacteria, propionibacteria and listeria, had potent adjuvant activity on immune responses. It was reported that N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP) was the minimum structural requirement of adjuvant activity of the bacterial cell-wall skeleton and a variety of MDP derivatives and related compounds were synthesized. Among the synthetic MDP derivatives, we have selected MDP-Lys(L18)(romurtide) as the immunostimulant, by using experimental models for non-specific host resistance against Escherichia coli in mice. Romurtide was shown to have host-stimulating activity against bacterial, fungal and viral infections, cytokine producing activity and the capacity to increase the number of leukocytes and platelets in experimental models. It was also shown that the clinical effectiveness of romurtide on the restoration of the number of leukocytes and platelets of cancer patients treated with chemotherapy or radiation therapy. The mechanism of action of romurtide is discussed.
我们已经报道过，细菌细胞壁骨架，如分枝杆菌、诺卡氏菌、棒状杆菌、丙酸杆菌和李斯特菌，对免疫反应具有强大的佐剂活性。据报道，N-乙酰胞壁酰-L-丙氨酰-D-异谷氨酰胺（MDP）是细菌细胞壁骨架佐剂活性的最小结构要求，并且合成了多种MDP衍生物及相关化合物。在合成的MDP衍生物中，我们通过使用小鼠对大肠杆菌的非特异性宿主抗性实验模型，选择了MDP-Lys(L18)（罗莫肽）作为免疫刺激剂。罗莫肽在实验模型中显示出对细菌、真菌和病毒感染的宿主刺激活性、细胞因子产生活性以及增加白细胞和血小板数量的能力。还表明罗莫肽对化疗或放疗治疗的癌症患者白细胞和血小板数量恢复具有临床有效性。本文讨论了罗莫肽的作用机制。
