Fluorofenidone protects mice from lethal endotoxemia through the inhibition of TNF-α and IL-1β release

被引：30

作者：

Tang, Yiting ^{[1
]}

Li, Bingxin ^{[1
]}

Wang, Nasui ^{[1
]}

Xie, Yanyun ^{[1
]}

Wang, Linghao ^{[1
]}

Yuan, Qiongjing ^{[1
]}

Zhang, Fangfang ^{[1
]}

Qin, Jiao ^{[1
]}

Peng, Zhangzhe ^{[1
]}

Ning, Wangbin ^{[1
]}

Wang, Ling ^{[1
]}

Hu, Gaoyun ^{[2
]}

Li, Jing

Tao, Lijian ^{[1
,3
]}

机构：

[1] Cent S Univ, Xiangya Hosp, Div Nephrol, Changsha 410008, Hunan, Peoples R China

[2] Cent S Univ, Fac Pharmaceut Sci, Changsha 410008, Hunan, Peoples R China

[3] Cent S Univ, State Key Lab Med Genet China, Changsha 410008, Hunan, Peoples R China

来源：

INTERNATIONAL IMMUNOPHARMACOLOGY | 2010年 / 10卷 / 05期

基金：

中国国家自然科学基金;

关键词：

Inflammation; Sepsis; Endotoxemia; SEPSIS; HMGB1; SURVIVAL;

D O I：

10.1016/j.intimp.2010.02.005

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

The pathogenesis of sepsis is mediated in part by bacterial endotoxin, which stimulates macrophages/monocytes to sequentially release proinflammatory factors like INF-alpha and IL-1 beta. Fluorofenidone (AKF-PD) is a novel pyridone agent, which exerts a strong antifibrotic effect. In this work, we showed that AKF-PD also exert an inhibitory effect on acute systemic inflammatory response. AKF-PD treatment significantly increased survival in animals with established endotoxemia. In addition, AKF-PD treatment significantly reduced circulating levels of TNF-alpha and IL-1 beta during endotoxemia. In macrophage cultures, AKF-PD inhibited the release of TNF-alpha and IL-1 beta in a dose-dependent manner. In conclusion, these results indicate that AKF-PD inhibits the release of the proinflammatory cytokines (TNF-alpha and IL-1 beta) and improves survival during lethal endotoxemia, which suggest this new pyridone agent can be a novel candidate for therapy of septic shock. (C) 2010 Elsevier B.V. All rights reserved.

引用

页码：580 / 583

页数：4

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