Interleukin-34 Ameliorates Survival and Bacterial Clearance in Polymicrobial Sepsis*

作者：Xue Lin, Hongchun Luo, Xingxing Yan, Zhixin Song, Xun Gao, Yun Xia, Liping Zhang, Yibing Yin, Ju Cao · 发表于：Critical Care Medicine · 年份：2018 · DOI：10.1097/ccm.0000000000003017 · 被引用次数：36 · 研究领域：Immune Cell Function and Interaction、Immune cells in cancer、IL-33, ST2, and ILC Pathways

OBJECTIVES: Sepsis is a devastating condition with a high mortality rate and limited treatments. Sepsis is characterized by a failed host immune response to contain the infection, resulting in organ dysfunction. Interleukin-34 is new cytokine involved in infection and immunity. Whether interleukin-34 is beneficial or deleterious to sepsis and the underlying mechanisms remains unknown. DESIGN: Prospective randomized animal investigation and in vitro studies. SETTING: Research laboratory at a university hospital. SUBJECTS: Wild-type C57BL/6 mice were used for in vivo studies, and septic human patients and healthy human subjects were used to obtain blood for in vitro studies. INTERVENTIONS: Interleukin-34 concentrations were measured in human sepsis patients and healthy individuals. The effects of interleukin-34 administration on survival, bacterial burden, organ injury, and inflammatory response were assessed in a murine model of cecal ligation and puncture-induced polymicrobial sepsis. MEASUREMENTS AND MAIN RESULTS: Interleukin-34 levels were significantly elevated in human sepsis and cecal ligation and puncture-induced experimental sepsis. Interleukin-34 administration improved survival and bacterial clearance, although suppressed vascular leakage and organ injury after cecal ligation and puncture-induced polymicrobial sepsis. Neutralization of interleukin-34 increased mortality rate and decreased bacterial clearance in septic mice. An increased neutrophil and macrophage infl...