Low-dose cisplatin administration to septic mice improves bacterial clearance and programs peritoneal macrophage polarization to M1 phenotype.
Sepsis 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.
The Department of Medical Oncology, Cancer Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
Yanyan
Y
Li
Zhenling
Z
Wang
Xuelei
X
Ma
Bin
B
Shao
Xiang
X
Gao
Binglan
B
Zhang
Guangchao
G
Xu
Yuquan
Y
Wei
D000818:Animals; D001419:Bacteria / Q000302:isolation & purification; D058491:Bacterial Load; D001769:Blood / Q000382:microbiology; D002454:Cell Differentiation / Q000187:drug effects*; D002945:Cisplatin / Q000008:administration & dosage*; D005260:Female; D007155:Immunologic Factors / Q000008:administration & dosage*; D015850:Interleukin-6 / Q000097:blood; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000276:immunology*; D008810:Mice, Inbred C57BL; D010529:Peritoneal Cavity / Q000382:microbiology; D010587:Phagocytosis / Q000187:drug effects; D018805:Sepsis / Q000188:drug therapy* / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D012720:Severity of Illness Index; D016019:Survival Analysis; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D007155:Immunologic Factors; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D002945:Cisplatin
bacterial clearance; cisplatin; peritoneal macrophage; phagocytosis; sepsis