101. 5-HT Drives Mortality in Sepsis Induced by Cecal Ligation and Puncture in Mice
- Author
-
Chang Liu, Sushun Liu, Qing Pang, Ruiyao Zhang, Jianbin Bi, Jingyao Zhang, and Shun Wang
- Subjects
Male ,0301 basic medicine ,Serotonin ,Article Subject ,Sepsis mortality ,animal diseases ,Immunology ,MEDLINE ,Punctures ,Tryptophan Hydroxylase ,Biology ,Bioinformatics ,Sepsis ,Mice ,03 medical and health sciences ,Text mining ,lcsh:Pathology ,medicine ,Animals ,Cecum ,Ligation ,5-HT receptor ,Mice, Knockout ,Interleukin-6 ,Tumor Necrosis Factor-alpha ,business.industry ,Cecal ligation ,Cell Biology ,bacterial infections and mycoses ,Serotonin metabolism ,medicine.disease ,Mice, Inbred C57BL ,Disease Models, Animal ,stomatognathic diseases ,030104 developmental biology ,business ,Research Article ,lcsh:RB1-214 - Abstract
Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection with a high mortality. 5-Hydroxytryptamine (5-HT) is an important regulatory factor in inflammation. The aim of this study is to investigate the role of 5-HT on cecal ligation and puncture- (CLP-) induced sepsis in the mouse model. CLP was performed on C57B/6 wild-type (WT) mice and tryptophan hydroxylase 1 (TPH1) knockout (KO) mice. The results showed that the 5-HT-sufficient group mice had a significantly lower survival rate than the 5-HT-deficient group in CLP-induced sepsis and septic shock. The KO-CLP sepsis group received a lower clinical score than the WT-CLP sepsis group. Meanwhile, the body temperature of mice in the KO-CLP sepsis group was higher than that in the WT-CLP sepsis group and was much closer to the normal body temperature 24 hours after CLP. The tissue histopathology analysis revealed that 5-HT markedly exacerbated histological damages in the peritoneum, lung, liver, kidney, intestinal tissue, and heart in sepsis. Moreover, significant lower levels of TNF-α, IL-6, bacterial loads, MPO, and ROS were discovered in the KO-CLP sepsis group in contrast to the WT-CLP sepsis group. In conclusion, 5-HT drives mortality and exacerbates organ dysfunction by promoting serum cytokines and bacterial loads as well as facilitating oxidative stress in the process of sepsis.
- Published
- 2017