Neutralisation of peritoneal IL-17A markedly improves the prognosis of severe septic mice by decreasing neutrophil infiltration and proinflammatory cytokines
Autor: | Miaoxia He, Jiali Zhu, Zailong Cai, Yan Zhang, Xiao-ming Deng, Jinbao Li, Jingsheng Lou |
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Jazyk: | angličtina |
Rok vydání: | 2012 |
Předmět: |
Male
Pathology medicine.medical_specialty Anatomy and Physiology Critical Care and Emergency Medicine Mouse Neutrophils medicine.medical_treatment Immunology Fluorescent Antibody Technique lcsh:Medicine Lung injury Proinflammatory cytokine Sepsis Peritoneal cavity Mice Model Organisms Immune Physiology Ascites medicine Animals lcsh:Science Biology Peritoneal Cavity Inflammation Multidisciplinary business.industry Peritoneal fluid Interleukin-17 lcsh:R Immunity Animal Models medicine.disease Flow Cytometry Prognosis Mice Inbred C57BL Cytokine medicine.anatomical_structure Cytokines Medicine lcsh:Q medicine.symptom Inflammation Mediators business Infiltration (medical) Research Article |
Zdroj: | PLoS ONE, Vol 7, Iss 10, p e46506 (2012) PLoS ONE |
ISSN: | 1932-6203 |
Popis: | 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. |
Databáze: | OpenAIRE |
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