Neutralisation of Peritoneal IL-17A Markedly Improves the Prognosis of Severe Septic Mice by Decreasing Neutrophil Infiltration and Proinflammatory Cytokines

作者：Li, Jinbao; Zhang, Yan; Lou, Jingsheng; Zhu, Jiali; He, Miaoxia; Deng, Xiaoming^*; Cai, Zailong

来源：PLos One, 2012, 7(10): e46506.

DOI：10.1371/journal.pone.0046506

• INFLAMMATORY RESPONSE SYNDROME
• SYNDROME SIRS
• LUNG INJURY
• T-CELLS
• SEPSIS
• INTERLEUKIN-17
• MECHANISMS
• MORTALITY

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-alpha, 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-alpha and IL-6 levels both in peritoneal fluid and blood, neutrophil infiltration in the peritoneal cavity, and lung injury. gamma delta 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 gamma delta 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.

• 出版日期2012-10-2
• 单位中国人民解放军总医院; 中国人民解放军第二军医大学