Interleukin 5 Is Protective during Sepsis in an Eosinophil-Independent Manner
Interleukin 5 Is Protective during Sepsis in an Eosinophil-Independent Manner
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DOI：
10.1164/rccm.201201-0134oc
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发表时间：
2012-08-01
影响因子：
24.7
通讯作者：
Gold, Jeffrey A.
中科院分区：
文献类型：
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作者：
Linch, Stefanie N.;Danielson, Erin T.;Gold, Jeffrey A.
理由：脓毒症的免疫反应的特点是明显的免疫功能障碍。研究表明免疫刺激对患者来说是一种可行的治疗方法。一项研究表明白细胞介素 5 (IL-5) 在脓毒症中具有潜在的保护作用；然而，这种疾病中嗜酸性粒细胞的丧失呈现出一个悖论。目的：评估IL-5在脓毒症中的保护作用和嗜酸性粒细胞独立作用。方法：我们评估了IL-5给药对多种微生物脓毒症后生存、细菌负荷和细胞因子产生的影响。此外，我们使用荧光显微镜和流式细胞术检查了对巨噬细胞吞噬作用和存活的影响。测量和主要结果：IL-5 的缺失增加了死亡率和肺部组织损伤、IL-6 和 IL-10 的产生以及败血症期间的细菌负荷。 IL-5 的治疗性给药可改善脓毒症的死亡率。有趣的是，IL-5 给药导致体内中性粒细胞募集。在嗜酸性粒细胞不存在的情况下，IL-5 过度表达可导致脓毒症死亡率降低，循环中性粒细胞和单核细胞增加，表明它们在 IL-5 保护作用中的重要性。此外，新数据证明脓毒症中中性粒细胞和单核细胞上有 IL-5 受体表达。 IL-5 增强巨噬细胞的细胞因子分泌、活化、吞噬作用和存活。重要的是，败血症发生前巨噬细胞的耗竭消除了 IL-5 介导的保护作用。 IL-5 的保护作用在人类中得到证实，脓毒症患者的 IL-5 水平升高。此外，患者的中性粒细胞和单核细胞表达 IL-5 受体。结论：综上所述，这些数据支持 IL-5 对非嗜酸性粒细胞骨髓细胞群体的新作用，并表明 IL-5 治疗可能是脓毒症的可行疗法。
Rationale: The immune response in sepsis is characterized by overt immune dysfunction. Studies indicate immunostimulation represents a viable therapy for patients. One study suggests a potentially protective role for interleukin 5 (IL-5) in sepsis; however, the loss of eosinophils in this disease presents a paradox.Objectives: To assess the protective and eosinophil-independent effects of IL-5 in sepsis.Methods: We assessed the effects of IL-5 administration on survival, bacterial burden, and cytokine production after polymicrobial sepsis. In addition, we examined the effects on macrophage phagocytosis and survival using fluorescence microscopy and flow cytometry.Measurements and Main Results: Loss of IL-5 increased mortality and tissue damage in the lung, IL-6 and IL-10 production, and bacterial burden during sepsis. Therapeutic administration of IL-5 improved mortality in sepsis. Interestingly, IL-5 administration resulted in neutrophil recruitment in vivo. IL-5 overexpression in the absence of eosinophils resulted in decreased mortality from sepsis and increased circulating neutrophils and monocytes, suggesting their importance in the protective effects of IL-5. Furthermore, novel data demonstrate IL-5 receptor expression on neutrophils and monocytes in sepsis. IL-5 augmented cytokine secretion, activation, phagocytosis, and survival of macrophages. Importantly, macrophage depletion before the onset of sepsis eliminated IL-5-mediated protection. The protective effects of IL-5 were confirmed in humans, where IL-5 levels were elevated in patients with sepsis. Moreover, neutrophils and monocytes from patients expressed the IL-5 receptor.Conclusions: Taken together, these data support a novel role for IL-5 on noneosinophilic myeloid populations, and suggest treatment with IL-5 may be a viable therapy for sepsis.