5-HT Drives Mortality in Sepsis Induced by Cecal Ligation and Puncture in Mice

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-...

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Main Authors: Jingyao Zhang, Jianbin Bi, Sushun Liu, Qing Pang, Ruiyao Zhang, Shun Wang, Chang Liu
Format: Article
Language:English
Published: Wiley 2017-01-01
Series:Mediators of Inflammation
Online Access:http://dx.doi.org/10.1155/2017/6374283
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author Jingyao Zhang
Jianbin Bi
Sushun Liu
Qing Pang
Ruiyao Zhang
Shun Wang
Chang Liu
author_facet Jingyao Zhang
Jianbin Bi
Sushun Liu
Qing Pang
Ruiyao Zhang
Shun Wang
Chang Liu
author_sort Jingyao Zhang
collection DOAJ
description 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.
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spelling doaj-art-a31a5a801763409282f8bb93f01d3f002025-02-03T05:52:08ZengWileyMediators of Inflammation0962-93511466-18612017-01-01201710.1155/2017/637428363742835-HT Drives Mortality in Sepsis Induced by Cecal Ligation and Puncture in MiceJingyao Zhang0Jianbin Bi1Sushun Liu2Qing Pang3Ruiyao Zhang4Shun Wang5Chang Liu6Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, ChinaDepartment of Hepatobiliary Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, ChinaDepartment of Hepatobiliary Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, ChinaDepartment of Hepatobiliary Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, ChinaDepartment of Hepatobiliary Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, ChinaDepartment of Cardiovascular Medicine, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, ChinaDepartment of Hepatobiliary Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, ChinaSepsis 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.http://dx.doi.org/10.1155/2017/6374283
spellingShingle Jingyao Zhang
Jianbin Bi
Sushun Liu
Qing Pang
Ruiyao Zhang
Shun Wang
Chang Liu
5-HT Drives Mortality in Sepsis Induced by Cecal Ligation and Puncture in Mice
Mediators of Inflammation
title 5-HT Drives Mortality in Sepsis Induced by Cecal Ligation and Puncture in Mice
title_full 5-HT Drives Mortality in Sepsis Induced by Cecal Ligation and Puncture in Mice
title_fullStr 5-HT Drives Mortality in Sepsis Induced by Cecal Ligation and Puncture in Mice
title_full_unstemmed 5-HT Drives Mortality in Sepsis Induced by Cecal Ligation and Puncture in Mice
title_short 5-HT Drives Mortality in Sepsis Induced by Cecal Ligation and Puncture in Mice
title_sort 5 ht drives mortality in sepsis induced by cecal ligation and puncture in mice
url http://dx.doi.org/10.1155/2017/6374283
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