Neutralisation of peritoneal IL-17A markedly improves the prognosis of severe septic mice by decreasing neutrophil infiltration and proinflammatory cytokines.
Neutralisation of peritoneal IL-17A markedly improves the prognosis of severe septic mice by decreasing neutrophil infiltration and proinflammatory cytokines.
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腹膜 IL-17A 的中和可通过减少中性粒细胞浸润和促炎细胞因子显着改善严重脓毒症小鼠的预后
DOI：
10.1371/journal.pone.0046506
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Cai Z
中科院分区：
文献类型：
--
作者：
Li J;Zhang Y;Lou J;Zhu J;He M;Deng X;Cai Z
目的探讨腹腔液IL-17A在脓毒症小鼠体内的作用，以及抗IL-17A抗体阻断IL-17A途径对小鼠盲肠结扎穿孔(CLP)脓毒症模型存活时间、血浆和腹膜细胞因子水平的影响。确定了脓毒症小鼠腹腔液IL-17A的主要来源。方法雄性C57BL/6小鼠接受严重CLP或假手术后，分别经腹腔或静脉注射抗IL17A抗体或同型抗体。观察两组动物的存活率。采用双抗体夹心法检测IL-17A、肿瘤坏死因子-α、IL-6细胞因子水平。流式细胞仪检测细胞表面和细胞内IL-17A免疫荧光染色以鉴定产生IL-17A的细胞。结果CLP小鼠腹腔液中IL-17A水平明显高于血液中IL-17A水平，且升高时间较早。由于腹腔液和血液中的肿瘤坏死因子-α和IL-6水平降低、中性粒细胞在腹膜腔内的渗出和肺损伤，因此，腹膜腔内阻断IL-17A对CLP所致的死亡有更明显的保护作用。γδT细胞是脓毒症小鼠腹腔液中IL-17A的主要来源。结论腹腔液中γδT细胞早期、高表达的IL-17A在多菌感染性严重脓毒症中起重要作用，腹腔注射IL-17A抗体对重症脓毒症小鼠存活的影响优于静脉注射。腹腔内阻断IL-17A可减少促炎细胞因子的产生，减少中性粒细胞的浸润，减少肺损伤，从而提高脓毒症小鼠的存活率，为脓毒症的治疗提供了新的潜在靶点。
Purpose The current study aimed to elucidate the role of peritoneal fluid IL-17A in septic mice, and the effects of intraperitoneal or intravenous blockade of the IL-17A pathway by anti-IL17A antibody on survival, plasma, and peritoneal cavity cytokine profile in a murine caecal ligation and puncture (CLP) sepsis model. The main source of peritoneal fluid IL-17A in septic mice was identified. Methods Male C57BL/6 mice that underwent severe CLP or sham surgery were intraperitoneally or intravenously administered anti-IL17A antibodies or isotype antibodies. The survival rates were observed. IL-17A, TNF-α, and IL-6 cytokine levels were measured by ELISA. Surface and intracellular IL-17A immunofluorescence stains were detected by flow cytometry to identify the IL-17A–producing cells. Results The IL-17A level was elevated much higher and earlier in peritoneal fluid than in the blood of the CLP mice. The intraperitoneal IL-17A blockade more significantly protects against CLP-induced mortality than intravenous blockade because of decreased TNF-α and IL-6 levels both in peritoneal fluid and blood, neutrophil infiltration in the peritoneal cavity, and lung injury. γδ T lymphocytes were identified to be the main source of IL-17A in the peritoneal fluid of septic mice. Conclusions The earlier and higher elevated IL-17A derived from γδ T cells in peritoneal fluid plays a critical role during polymicrobial severe sepsis and effect of intraperitoneal IL-17A antibody administration superior to intravenous administration on survival of severe CLP-induced septic mice. The intraperitoneal blockade of IL-17A decreases proinflammatory cytokine production, neutrophil infiltration, and lung injury, thereby improving septic mice survival, which provides a new potential therapy target for sepsis.
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影响因子：
64.5
作者：
Ivanov, Ivaylo I.;McKenzie, Brent S.;Littman, Dan R.
通讯作者：
Littman, Dan R.
影响因子：
--
作者：
Bosmann, Markus;Ward, Peter A.
通讯作者：
Ward, Peter A.
影响因子：
4.8
作者：
Flierl, Michael A.;Rittirsch, Daniel;Ward, Peter A.
通讯作者：
Ward, Peter A.
影响因子：
4.4
作者：
Freitas, Andressa;Alves-Filho, Jose C.;Ryffel, Bernhard
通讯作者：
Ryffel, Bernhard
DOI：
10.1159/000324024
发表时间：
2011-01-01
期刊：
SEPSIS - PRO-INFLAMMATORY AND ANTI-INFLAMMATORY RESPONSES: GOOD, BAD OR UGLY?
影响因子：
--
作者：
Shubin, Nicholas J.;Monaghan, Sean F.;Ayala, Alfred
通讯作者：
Ayala, Alfred