Interleukin-6 treatment reverses apoptosis and blunts susceptibility to intraperitoneal bacterial challenge following hemorrhagic shock.
Interleukin-6 treatment reverses apoptosis and blunts susceptibility to intraperitoneal bacterial challenge following hemorrhagic shock.
复制标题
Interleukin-6 治疗可逆转细胞凋亡并降低失血性休克后对腹膜内细菌攻击的敏感性。
DOI：
10.1097/01.ccm.0000201901.30292.c2
复制
发表时间：
2006
影响因子：
8.8
通讯作者：
Tweardy,DavidJ
中科院分区：
文献类型：
--
作者：
Arikan,AyseAkcan;Yu,Bi;Mastrangelo,Mary-Ann;Tweardy,DavidJ
Background:Resuscitation from hemorrhagic shock (HS) predisposes to subsequent infections. Susceptibility to infection following sepsis has been attributed to apoptosis. Interleukin (IL)-6 has been shown to have antiapoptotic properties and to decrease postresuscitation inflammation in rodent and porcine models of HS.Objective:The objective was to determine if HS increases host susceptibility to infection, if IL-6 administration at resuscitation reduces this susceptibility, and if changes in susceptibility to infection are accompanied by parallel changes in apoptosis.Subjects and Interventions:Mice were randomized into three groups—HS, sham, and no-surgery control—and each group was further randomized to receive either IL-6 (3 μg/kg; HS/IL-6) or placebo (HS/P) at the start of resuscitation. In the HS-infection protocol, each mouse was challenged intraperitoneally the next day with a sublethal dose of Staphylococcus aureus (4× 10 7 colony-forming units); 24 hrs later, the peritoneal cavity was lavaged and the major organs were harvested for culture. In the HS-apoptosis protocol, the livers were harvested the next day and analyzed by means of the terminal deoxynucleotidyl transferase dUTP-biotin nick-end-labeling (TUNEL) assay.Results:HS/P mice had a six-to eight-fold increase in total bacterial counts in comparison with sham and control mice that was attributable to a seven-to nine-fold increase in liver burden. IL-6 treatment reduced total and liver bacterial counts in HS/IL-6 mice by 62% and 69%, respectively, to levels statistically indistinguishable from IL-6-treated sham and control mice. The number of TUNEL-positive liver cells in the HS/P group was increased eight-fold vs. that in the sham group (p=. 002); IL-6 resuscitation completely reversed the HS-induced increase in TUNEL-positive cells in the HS/IL-6 group (p=. 002).Conclusions:IL-6 treatment at resuscitation eliminated the HS-mediated increase in total and liver bacterial burden and protected the liver from HS-induced apoptosis. Reduced liver apoptosis may explain the ability of IL-6 to blunt the HS-induced increase in susceptibility to bacterial challenge.
