Lethality during continuous anthrax lethal toxin infusion is associated with circulatory shock but not inflammatory cytokine or nitric oxide release in rats
Lethality during continuous anthrax lethal toxin infusion is associated with circulatory shock but not inflammatory cytokine or nitric oxide release in rats
复制标题
DOI：
10.1152/ajpregu.00593.2003
复制
发表时间：
2004-04-01
影响因子：
2.8
通讯作者：
Eichacker, PQ
中科院分区：
文献类型：
--
作者：
Cui, XZ;Moayeri, M;Eichacker, PQ
虽然致死毒素相关的循环休克（LeTx）可能在炭疽杆菌感染致死中起主要作用，但其机制尚不清楚。我们研究了LeTx诱导的休克是否与炎性细胞因子和一氧化氮（NO）的释放有关。带有中心静脉和动脉导管的Sprague-Dawley大鼠接受24小时LeTx输注（致死因子100 μ g/kg;保护性抗原200 μ g/kg），从9小时开始产生死亡，7天死亡率为53%。到9小时，与LeTx幸存者和对照组（仅稀释剂）相比，LeTx非幸存者的平均动脉血压、心率、pH和碱过剩降低，乳酸盐和血红蛋白水平升高（3组比较，P均小于或等于0.05）。尽管有这些变化，动脉血氧和循环白细胞和血小板没有减少，TNF-α，IL-1 β，IL-6和IL-10水平没有增加，比较LeTx非幸存者或幸存者与对照组。硝酸盐/亚硝酸盐水平和组织组织学也没有差异比较LeTx动物和对照组。在另外的实验中，虽然24小时输注LeTx和大肠杆菌LPS产生了相似的死亡率，（分别为54%和56%）和死亡时间（分别为13.2 +/- 0.8 vs. 11.0 +/- 1.7 h）与对照组相比，只有LPS降低了循环白细胞、血小板和IL-2水平，增加了TNF-α、IL-1 α和IL-1 β，IL-6、IL-10、干扰素-γ、粒细胞巨噬细胞集落刺激因子、RANTES、迁移抑制蛋白-1 α、-2和-3和单核细胞趋化蛋白-1，以及硝酸盐/亚硝酸盐水平（LPS作用的所有P均小于或等于0.05）。因此，与LPS相反，过量的炎性细胞因子和NO释放似乎不会导致该大鼠模型中LeTx发生的循环休克和致死性。虽然调节这些宿主介质的疗法可能适用于LPS或其他细菌毒素引起的休克，但它们可能不适用于LeTx。
Although circulatory shock related to lethal toxin (LeTx) may play a primary role in lethality due to Bacillus anthracis infection, its mechanisms are unclear. We investigated whether LeTx-induced shock is associated with inflammatory cytokine and nitric oxide ( NO) release. Sprague-Dawley rats with central venous and arterial catheters received 24-h infusions of LeTx ( lethal factor 100 mug/kg; protective antigen 200 mug/kg) that produced death beginning at 9 h and a 7-day mortality rate of 53%. By 9 h, mean arterial blood pressure, heart rate, pH, and base excess were decreased and lactate and hemoglobin levels were increased in LeTx nonsurvivors compared with LeTx survivors and controls ( diluent only) ( P less than or equal to 0.05 for each comparing the 3 groups). Despite these changes, arterial oxygen and circulating leukocytes and platelets were not decreased and TNF-alpha, IL-1beta, IL-6, and IL-10 levels were not increased comparing either LeTx nonsurvivors or survivors to controls. Nitrate/nitrite levels and tissue histology also did not differ comparing LeTx animals and controls. In additional experiments, although 24-h infusions of LeTx and Esherichia coli LPS produced similar mortality rates ( 54 and 56%, respectively) and times to death (13.2 +/- 0.8 vs. 11.0 +/- 1.7 h, respectively) compared with controls, only LPS reduced circulating leukocytes, platelets, and IL-2 levels and increased TNF-alpha, IL-1alpha and - 1beta, IL-6, IL-10, interferon-gamma, granulocyte macrophage-colony stimulating factor, RANTES, migratory inhibitory protein-1alpha, - 2, and - 3, and monocyte chemotactic protein-1, as well as nitrate/nitrite levels ( all P less than or equal to 0.05 for the effects of LPS). Thus, in contrast to LPS, excessive inflammatory cytokine and NO release does not appear to contribute to the circulatory shock and lethality occurring with LeTx in this rat model. Although therapies to modulate these host mediators may be applicable for shock caused by LPS or other bacterial toxins, they may not with LeTx.