Cui Xizhong, Moayeri Mahtab, Li Yan, Li Xuemei, Haley Michael, Fitz Yvonne, Correa-Araujo Rosaly, Banks Steven M, Leppla Stephen H, Eichacker Peter Q
Critical Care Medicine Department, National Institutes of Health, Bldg. 10, Rm. 7D43, Bethesda, MD 20892, USA.
Am J Physiol Regul Integr Comp Physiol. 2004 Apr;286(4):R699-709. doi: 10.1152/ajpregu.00593.2003. Epub 2004 Jan 8.
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 microg/kg; protective antigen 200 microg/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 < or = 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-beta, 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 Escherichia 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-1 alpha and -1 beta, IL-6, IL-10, interferon-gamma, granulocyte macrophage-colony stimulating factor, RANTES, migratory inhibitory protein-1 alpha, -2, and -3, and monocyte chemotactic protein-1, as well as nitrate/nitrite levels (all P < or = 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 at model. Although therapies to modulate these host mediators may be applicable fo shock caused by LPS or other bacterial toxins, they may not with LeTx.
尽管与致死毒素（LeTx）相关的循环性休克可能在炭疽杆菌感染致死过程中起主要作用，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）释放有关。将带有中心静脉和动脉导管的Sprague-Dawley大鼠接受24小时的LeTx输注（致死因子100微克/千克；保护性抗原200微克/千克），输注开始9小时后出现死亡，7天死亡率为53%。到9小时时，与LeTx存活者和对照组（仅稀释剂）相比，LeTx非存活者的平均动脉血压、心率、pH值和碱剩余降低，乳酸和血红蛋白水平升高（三组比较，每组P≤0.05）。尽管有这些变化，但与对照组相比，LeTx非存活者或存活者的动脉血氧、循环白细胞和血小板并未减少，TNF-α、IL-β、IL-6和IL-10水平也未升高。比较LeTx动物和对照组，硝酸盐/亚硝酸盐水平和组织组织学也没有差异。在另外实验中，尽管与对照组相比，24小时输注LeTx和大肠杆菌脂多糖（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小时和11.0±1.7小时），但只有LPS降低了循环白细胞、血小板和IL-2水平，并增加了TNF-α、IL-1α和-1β、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-1α、-2和-3以及单核细胞趋化蛋白-1，以及硝酸盐/亚硝酸盐水平（LPS的所有效应P≤0.05）。因此，与LPS相反，在该动物模型中，过量的炎性细胞因子和NO释放似乎并不导致LeTx引起的循环性休克和致死。尽管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引起的休克。
