Abstract
PurposeThe 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.MethodsMale 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.ResultsThe 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.ConclusionsThe 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.
Highlights
Sepsis is a clinical syndrome resulting from the systemic inflammatory response to a variety of bacterial infections
The peak IL17A concentration appeared at 12 h, and a rapid decline to the baseline values occurred at 24 h (Figure 1A)
In peritoneal lavage fluid from all caecal ligation and puncture (CLP) mice, the IL-17A level markedly increased 6 h after CLP compared with the sham mice, earlier than the time at which IL-17A was elevated in the blood
Summary
Sepsis is a clinical syndrome resulting from the systemic inflammatory response to a variety of bacterial infections. The high rates of morbidity and mortality of sepsis may result from a failure of initial pathogenic clearance or susceptibility to a secondary infection, both of which result in end-organ tissue damage. Numerous studies have demonstrated that an aberrant innate immune response early in sepsis leads to end-organ damage [1,2]. The onset of the adaptive response to bacterial infection is thought to occur after the innate response has subsided and to maintain surveillance as well as prevent new infections [3,4]. A recently emerging view points out that adaptive immune responses may be engaged much earlier in sepsis than previously thought [5]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
