• Xue Lin, Hongchun Luo, Xingxing Yan, Zhixin Song, Xun Gao, Yun Xia, Liping Zhang, Yibing Yin, and Ju Cao.
• Department of Laboratory Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
• Crit. Care Med. 2018 Jun 1; 46 (6): e584-e590.

ObjectivesSepsis 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.DesignProspective randomized animal investigation and in vitro studies.SettingResearch laboratory at a university hospital.SubjectsWild-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.InterventionsInterleukin-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 ResultsInterleukin-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 influx were developed in interleukin-34-treated mice at the site of infection, accompanied by elevated production of neutrophil chemokine chemokine (C-X-C motif) ligand 1 and macrophage chemokine C-C motif chemokine ligand 2 in the peritoneal cavity. Depletion of neutrophils or macrophages reversed interleukin-34-mediated protection against polymicrobial sepsis.ConclusionsWe reported for the first time a potential therapeutic role for interleukin-34 in sepsis and suggested that interleukin-34 is a novel target for the development of therapeutic agents against sepsis.

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