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Exp Ther Med. 2018 Jul;16(1):171-177. doi: 10.3892/etm.2018.6181. Epub 2018 May 17.

Effect of interleukin-31 on septic shock through regulating inflammasomes and interleukin-1β.

Author information

1
Department of Critical Care Medicine, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, P.R. China.
2
Department of Cancer Chemotherapy, Peking University First Hospital, Beijing 100038, P.R. China.

Abstract

Sepsis with severe systemic inflammation remains a great challenge for the intensive care unit in clinics. Although biomarkers have been identified to diagnose, monitor and predict these syndromes, novel therapeutic approaches are required for the amelioration of symptoms of sepsis and septic shock. The present study demonstrated that interleukin (IL)-31 was able reduce the mortality rate of lipopolysaccharide (LPS)-induced sepsis with the reduction of inflammatory cytokines in the sera. IL-31 also inhibited IL-1β production in the peritoneal lavage fluid in LPS-induced or cecal ligation and puncture-induced sepsis. The in vitro mechanism responsible for IL-31 regulation on peritoneal IL-1β activation following LPS challenge was explored. It was demonstrated that IL-1β secretion was suppressed by IL-31 treatment from LPS-challenged peritoneal macrophages following adenosine triphosphate stimulation, which is an activator of NLR family, pyrin domain-containing 3 (NLRP3). Furthermore, IL-31 inhibited the expression of NLRP3 at the transcriptional level. In human THP-1 cells, anti-IL-31/anti-IL-31 receptor (R) neutralizing antibody enhanced NLRP3 expression as well as IL-1β activation, suggesting a role of the IL-31-IL-31R-NLRP3-IL-1β signaling axis in the physiological status of sepsis. On the other hand, IL-31 displayed a negative effect on the NLRP1 inflammasome, but not on NLRP3 on the LPS-primed human peripheral blood monocytes, resulting in reduction of the inflammatory cytokine, tumor necrosis factor (TNF)-α, in the supernatant. Taken together, the present data implied that T helper 2-type cytokine, IL-31, may be a promising therapeutic option for treatment of sepsis and septic shock in clinics.

KEYWORDS:

NLR family; NLRP3; inflammasomes; interleukin-1β; interleukin-31; pyrin domain-containing 3; sepsis

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