Interleukin-34 Ameliorates Survival and Bacterial Clearance in Polymicrobial Sepsis
Interleukin-34 Ameliorates Survival and Bacterial Clearance in Polymicrobial Sepsis
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Interleukin-34 改善多种微生物败血症的存活率和细菌清除率
DOI：
10.1097/ccm.0000000000003017
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发表时间：
2018-06-01
影响因子：
8.8
通讯作者：
Cao, Ju
中科院分区：
文献类型：
--
作者：
Lin, Xue;Luo, Hongchun;Cao, Ju
目标：败血症是一种毁灭性的疾病，死亡率高，治疗方法有限。脓毒症的特征在于宿主免疫应答失败以遏制感染，导致器官功能障碍。白细胞介素-34（IL-34）是一种新的参与感染和免疫的细胞因子。白细胞介素-34对脓毒症是有益还是有害以及潜在的机制仍然未知。设计：前瞻性随机动物调查和体外研究。设置：大学医院的研究实验室。受试者：野生型C57 BL/6小鼠用于体内研究，脓毒症患者和健康人受试者用于获得血液用于体外研究。干预措施：在人脓毒症患者和健康个体中测量白细胞介素-34浓度。白细胞介素-34管理对生存，细菌负荷，器官损伤和炎症反应的影响进行了评估，在盲肠结扎和穿刺诱导的polymicrobial sepsis. Measures和主要结果：白细胞介素-34水平显着升高，在人类脓毒症和盲肠结扎和穿刺诱导的实验性脓毒症的小鼠模型。白细胞介素-34管理改善生存和细菌清除，虽然抑制血管渗漏和器官损伤后盲肠结扎和穿刺诱导的多微生物败血症。白细胞介素-34的中和增加了败血症小鼠的死亡率并降低了细菌清除率。白细胞介素-34治疗的小鼠在感染部位出现了增加的中性粒细胞和巨噬细胞流入，同时腹腔中中性粒细胞趋化因子趋化因子（C-X-C基序）配体1和巨噬细胞趋化因子C-C基序趋化因子配体2的产生增加。耗尽中性粒细胞或巨噬细胞逆转白细胞介素-34介导的保护对polymicrobial separation.Conclusions：我们首次报道了一个潜在的治疗作用，白细胞介素-34在脓毒症，并建议白细胞介素-34是一个新的目标，为发展的治疗药物对脓毒症。
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 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.Conclusions: We 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.