Nakajima R, Namba K, Ishida Y, Katsuma E, Otani T, Osada Y
Exploratory Research Laboratories I, Daiichi Pharmaceutical Co., Ltd., Tokyo, Japan.
Chemotherapy. 1992;38(4):238-50. doi: 10.1159/000239007.
The anti-infective activity of romurtide, a synthetic muramyl dipeptide (MDP) derivative, was evaluated in experimental pneumococcal pneumonia in mice deficient in the third component of complement (C3). The compound was found to be effective against the pneumonia in combination with subcutaneous ampicillin (ABPC). This synergistic effect of romurtide with ABPC was most pronounced when the compound was administered subcutaneously 1 day before infection. Romurtide alone, however, was not effective, irrespective of its treatment timing. Similarly, consecutive treatment with ABPC alone failed to kill pneumococci in the lungs completely, and resultant regrowth of the organisms provoked purulent pneumonia. In contrast, the combination treatment of romurtide with ABPC successfully prevented most of the mice from the purulent pneumonia: the initial infiltration of resident alveolar macrophages and subsequent accumulation of macrophages were observed in the pneumonic foci. In accordance with the occurrence of these cellular responses in the lungs, pneumococci were successfully eliminated from the lungs in mice treated with romurtide in combination with ABPC. Thus, romurtide was suggested to promote recovery of the mice with pneumococcal pneumonia by activating resident and accumulated macrophages in the pneumonic foci to eliminate pneumococci from the lung.
在缺乏补体第三成分（C3）的小鼠实验性肺炎模型中，评估了合成的胞壁酰二肽（MDP）衍生物罗穆肽的抗感染活性。发现该化合物与皮下注射氨苄西林（ABPC）联合使用时对肺炎有效。当在感染前1天皮下给药罗穆肽时，其与ABPC的这种协同作用最为明显。然而，单独使用罗穆肽无效，无论其治疗时机如何。同样，单独连续使用ABPC也不能完全杀死肺中的肺炎球菌，细菌的再生长会引发脓性肺炎。相比之下，罗穆肽与ABPC联合治疗成功地使大多数小鼠免于脓性肺炎：在肺炎病灶中观察到驻留肺泡巨噬细胞的初始浸润以及随后巨噬细胞的聚集。与肺中这些细胞反应的发生一致，在用罗穆肽与ABPC联合治疗的小鼠中，肺炎球菌成功地从肺中清除。因此，提示罗穆肽通过激活肺炎病灶中的驻留和聚集巨噬细胞以从肺中清除肺炎球菌，从而促进肺炎球菌肺炎小鼠的恢复。
