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Pathogens and disease · Nov 2014
Low-dose cisplatin administration to septic mice improves bacterial clearance and programs peritoneal macrophage polarization to M1 phenotype.
- Yanyan Li, Zhenling Wang, Xuelei Ma, Bin Shao, Xiang Gao, Binglan Zhang, Guangchao Xu, and Yuquan Wei.
- The Department of Medical Oncology, Cancer Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
- Pathog Dis. 2014 Nov 1;72(2):111-23.
AbstractSepsis is a systemic inflammatory response to infection, and early responses of macrophages are vital in controlling the infected microorganisms. We used a cecal ligation and puncture (CLP) model of sepsis to determine the role of cisplatin (0.1, 0.5 and 1 mg kg(-1)) with respect to peritoneal macrophages, controlling peritoneal/blood bacterial infection, and systemic inflammation. We found that mice which received low-dose (0.1 and 0.5 mg kg(-1)) i.p. cisplatin had lower mortality rate and improved clinical scores compared with mice in normal saline-treated group, and the level of IL-6 and TNF-α was significantly reduced after cisplatin administration in peritoneal fluid of mice underwent CLP. Although cisplatin had no directly bactericidal ability, the numbers of bacteria in peritoneal and blood were significantly reduced at 24 and 72 h after the onset of CLP. Besides, in vivo phagocytosis and killing assay showed that the ability of macrophage derived from peritoneum was significantly increased with cisplatin treatment (5, 10, and 15 μM) for both gram-positive (Enterococcus faecalis) and gram-negative (Escherichia coli) bacteria. This was associated with the macrophage phenotype polarization from CD11b(+) F4/80(high) CD206(-) to CD11b(+) F4/80(low) CD206(-) M1 group. These findings underscore the importance of low-dose cisplatin in the treatment of sepsis.© 2014 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.
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