Interleukin 36α Attenuates Sepsis by Enhancing Antibacterial Functions of Macrophages
Interleukin 36α Attenuates Sepsis by Enhancing Antibacterial Functions of Macrophages
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白细胞介素 36α 通过增强巨噬细胞的抗菌功能来减轻脓毒症
DOI：
10.1093/infdis/jiw535
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发表时间：
2017-01-15
影响因子：
6.4
通讯作者：
Cao, Ju
中科院分区：
文献类型：
--
作者：
Tao, Xintong;Song, Zhixin;Cao, Ju
背景资料。脓毒症是一种因宿主对感染的反应失调而导致的危及生命的器官功能障碍，死亡率高，有效治疗有限。白介素36α(IL-36α)在脓毒症时宿主反应中的作用尚不清楚。建立盲肠结扎穿孔脓毒症模型，观察IL-36α对脓毒症宿主反应的影响。IL-36α的产生在脓毒症期间显著上调。IL-36α治疗可降低盲肠结扎和穿孔所致严重脓毒症小鼠的死亡率。IL-36α处理的小鼠有更有效的细菌清除，抑制组织炎症，改善器官损伤，并减少免疫细胞凋亡。IL-36α的特异性阻断导致非严重脓毒症小鼠死亡率增加，这一发现也突显了这些观察的治疗意义。此外，我们发现IL-36α增强了巨噬细胞对细菌的吞噬和杀伤作用，从而允许局部和全身细菌清除。重要的是，脓毒症发作前巨噬细胞的耗尽消除了IL-36α介导的对脓毒症的保护。我们的结果表明，IL-36α在脓毒症的宿主防御反应中发挥重要作用，并提示IL-36α在脓毒症中的潜在治疗作用。
Background. Sepsis is newly defined as life-threatening organ dysfunction caused by a dysregulated host response to infection with a high mortality rate and limited effective treatments. The role of interleukin 36 alpha (IL-36 alpha) in host response during sepsis remains unknown.Methods. An experimental sepsis model of cecal ligation and puncture was established to investigate the effects of IL-36 alpha on host response to sepsis.Results. IL-36 alpha production was significantly up-regulated during sepsis. IL-36 alpha treatment reduced the mortality rate in mice with severe sepsis by cecal ligation and puncture. IL-36 alpha-treated mice had more efficient bacterial clearance, inhibited tissue inflammation, improved organ injury, and reduced immune cell apoptosis. The therapeutic implication of these observations was also highlighted by the finding that specific blockade of IL-36 alpha led to an increased mortality rate in mice with nonsevere sepsis. Furthermore, we found that IL-36 alpha enhanced bacterial phagocytosis and killing by macrophages, thereby allowing local and systemic bacterial clearance. Importantly, macrophage depletion before the onset of sepsis eliminated IL-36 alpha-mediated protection against sepsis.Conclusions. Our results demonstrate that IL-36 alpha plays an important role in the host defense response to sepsis and suggest a potential therapeutic role for IL-36 alpha in sepsis.