Niu Hui, Yang Tianli, Wang Jin, Wang Rui, Cai Yun
Department of Pharmacy, Center of Medicine Clinical Research, Medical Supplies Center of PLA General Hospital, Beijing, China.
Front Pharmacol. 2021 Jan 20;11:602054. doi: 10.3389/fphar.2020.602054. eCollection 2020.
Colistin is the last resort of antimicrobials against multi-drug resistant Gram-negative pathogens. Previous studies in and macrophages of rats have suggested that colistin possesses the immunomodulatory properties by acting p38/MAPK pathway. Here, we aimed to confirm the immunomodulatory role of colistin in animal models. Rat model of Methicillin-resistant (MRSA)-induced pneumonia was established. Plasma concentrations of proinflammatory cytokines, quantitative bacteriology, histology and immunohistochemistry of lungs were assessed to compare the immunomodulatory properties of colistin pre-administration. The numbers of white blood cells and granulocytes were significantly increased in the 9 mg/kg colistin pre-administration group at 72 h after infection. Levels of TNF-α, IL-6 and IL-1β in plasma after colistin pre-administration were lower compared with the infected group without treatment. Colistin pre-treatment resulted in lower bacterial counts, a dramatic decrease of cytokines and improved histopathological injury in infected lung tissues compared with the untreated animals. However, p38/MAPK inhibitor SB203580 did not fully block the above-mentioned effects caused by colistin. Pre-administration of colistin could attenuate an excessive inflammatory reaction and protect the lungs from MRSA-associated damages. However, these effects could not be reversed by blocking the p38/MAPK pathway alone. Collectively, the mechanism underlying the immunoregulatory effects of colistin in mammals needs to be further explored.
黏菌素是对抗多重耐药革兰氏阴性病原体的最后一道抗菌防线。先前在大鼠的[具体实验对象未明确]和巨噬细胞中的研究表明，黏菌素通过作用于p38/丝裂原活化蛋白激酶（MAPK）途径具有免疫调节特性。在此，我们旨在证实黏菌素在动物模型中的免疫调节作用。建立了耐甲氧西林金黄色葡萄球菌（MRSA）诱导的大鼠肺炎模型。评估了促炎细胞因子的血浆浓度、定量细菌学、肺组织学和免疫组织化学，以比较预先给予黏菌素的免疫调节特性。在感染后72小时，预先给予9毫克/千克黏菌素的组中白细胞和粒细胞数量显著增加。与未治疗的感染组相比，预先给予黏菌素后血浆中肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）和白细胞介素-1β（IL-1β）的水平较低。与未治疗的动物相比，预先给予黏菌素导致感染肺组织中的细菌计数降低、细胞因子显著减少以及组织病理学损伤改善。然而，p38/MAPK抑制剂SB203580并未完全阻断黏菌素引起的上述效应。预先给予黏菌素可减轻过度的炎症反应并保护肺部免受MRSA相关损伤。然而，仅通过阻断p38/MAPK途径并不能逆转这些效应。总体而言，黏菌素在哺乳动物中的免疫调节作用机制有待进一步探索。
