Sublethal doses of Bacillus anthracis lethal toxin inhibit inflammation with lipopolysaccharide and Escherichia coli challenge but have opposite effects on survival
Sublethal doses of Bacillus anthracis lethal toxin inhibit inflammation with lipopolysaccharide and Escherichia coli challenge but have opposite effects on survival
复制标题
DOI：
10.1086/500468
复制
发表时间：
2006-03-15
影响因子：
6.4
通讯作者：
Eichacker, PQ
中科院分区：
文献类型：
--
作者：
Cui, XZ;Li, Y;Eichacker, PQ
背景。在前人体外实验的基础上，我们推测炭疽致死毒素（LeTx）在体内具有抗炎作用。我们研究了亚致死剂量LeTx对大鼠血管内脂多糖（LPS）或气管内大肠杆菌（Escherichia coli）攻击的影响。在LPS输注24小时的大鼠中，与对照大鼠相比，在输注前3小时预处理高或低亚致死剂量的LeTx，在168小时存活风险比（HR）的降低模式相似（0.60[95%可信区间{CI}， 0.37-0.98];，对于联合剂量）。LeTx在LPS输注期间平均动脉血压升高（P = .001）；降低13种细胞因子（即白细胞介素[IL]-1 α， IL-1 β, IL-2, IL-4, IL-6, IL-10，干扰素γ，肿瘤坏死因子α，粒细胞巨噬细胞集落刺激因子，迁移抑制蛋白[MIP]-1 α， MIP-2， MIP-3 α和RANTES）在2小时的水平；8 h时13种细胞因子水平均降低；24 h时仅降低4种细胞因子水平；并在8 h和24 h降低血浆一氧化氮（NO）水平，但在2 h没有降低(P
Background. On the basis of the findings of previous in vitro studies, we hypothesized that anthrax lethal toxin (LeTx) would have anti-inflammatory effects in vivo.Methods. We investigated the effects of sublethal doses of LeTx in rats receiving intravascular challenge with lipopolysaccharide (LPS) or intratracheal challenge with Escherichia coli.Results. In rats receiving 24-h infusions of LPS, compared with control rats, pretreatment with high or low sublethal doses of LeTx 3 h before infusion produced similar patterns of reduction in the hazards ratio (HR) of survival at 168 h (0.60 [95% confidence interval {CI}, 0.37-0.98];, for the doses combined). LeTx increased mean arterial blood pressure throughout the period of LPS infusion (P = .001); decreased the levels of 10 of 13 cytokines assessed (i.e., interleukin [IL]-1 alpha, IL-1 beta, IL-2, IL-4, IL-6, IL-10, interferon-gamma, tumor necrosis factor-alpha, granulocyte macrophage-colony-stimulating factor, migratory inhibitory protein [MIP]-1 alpha, MIP-2, MIP-3 alpha, and RANTES) at 2 h; decreased all 13 cytokine levels at 8 h; decreased only 4 cytokine levels at 24 h; and decreased the plasma level of nitric oxide (NO) at 8 h and 24 h but not at 2 h (P