IFN-gamma involvement in the severity of gram-negative infections in mice.
IFN-gamma involvement in the severity of gram-negative infections in mice.
复制标题
IFN-γ 与小鼠革兰氏阴性菌感染的严重程度有关。
DOI：
10.4049/jimmunol.151.2.916
复制
发表时间：
1993
影响因子：
4.4
通讯作者：
M. Glauser
中科院分区：
文献类型：
--
作者：
J. Kohler;D. Heumann;G. Garotta;D. Leroy;S. Bailat;C. Barras;J. Baumgartner;M. Glauser
IFN-γ在导致革兰氏阴性脓毒性休克的炎症调节中的作用仍然知之甚少。IFN-γ阻断已显示出改善用LPS和革兰氏阴性细菌的静脉内推注攻击的动物的存活率。我们研究了一种局灶性大肠杆菌感染导致腹膜炎和感染性休克的模型。用接近LD 50的接种物腹膜内攻击小鼠。rIFN-γ与细菌一起添加增加了死亡率和血液TNF-α和IL-6的水平。相反，用中和mAb阻断IFN-γ显著改善了小鼠的存活率。这种有益作用与存活者血液细菌计数和TNF-α和IL-6水平的严格降低无关。在该模型中，抗IFN-γ mAb的保护作用与中和抗TNF-α mAb的无效性形成对比。这些发现表明，在局灶性革兰氏阴性菌感染期间，IFN-γ的过度产生可能比TNF-α的过度产生具有更有害的作用。
The role of IFN-gamma in the regulation of inflammation leading to gram-negative septic shock is still poorly understood. IFN-gamma blockade has been shown to improve the survival of animals challenged with i.v. bolus injections of LPS and gram-negative bacteria. We have investigated a model of focal Escherichia coli infection leading to peritonitis and septic shock. Mice were challenged i.p. with an inoculum near the LD50. The addition of rIFN-gamma together with bacteria increased the mortality and the level of blood TNF-alpha and IL-6. Conversely blockade of IFN-gamma with a neutralizing mAb significantly improved the survival of the mice. This beneficial effect was not associated with a stringent decrease in blood bacterial counts and TNF-alpha and IL-6 levels in survivors. In this model, the protective effect of anti-IFN-gamma mAb contrasted with the ineffectiveness of a neutralizing anti-TNF-alpha mAb. These findings suggest that overproduction of IFN-gamma might have a more detrimental role than overproduction of TNF-alpha during focal gram-negative infections.