Neutralisation of peritoneal IL-17A markedly improves the prognosis of severe septic mice by decreasing neutrophil infiltration and proinflammatory cytokines.
OBJECTIVE
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.
Department of Anesthesiology, Changhai Hospital, Second Military Medical University, Shanghai, China.
Jinbao
J
Li
Yan
Y
Zhang
Jingsheng
J
Lou
Jiali
J
Zhu
Miaoxia
M
He
Xiaoming
X
Deng
Zailong
Z
Cai
D000818:Animals; D016207:Cytokines / Q000378:metabolism*; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D018836:Inflammation Mediators / Q000378:metabolism*; D020381:Interleukin-17 / Q000037:antagonists & inhibitors*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000502:physiology*; D010529:Peritoneal Cavity / Q000503:physiopathology*; D011379:Prognosis; D018805:Sepsis / Q000503:physiopathology*
D016207:Cytokines; D018836:Inflammation Mediators; D020381:Interleukin-17