Role of tumor necrosis factor alpha in gnotobiotic mice infected with an Escherichia coli O157:H7 strain
Role of tumor necrosis factor alpha in gnotobiotic mice infected with an Escherichia coli O157:H7 strain
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DOI：
10.1128/iai.66.1.197-202.1998
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发表时间：
1998-01-01
影响因子：
3.1
通讯作者：
Takeshi, K
中科院分区：
文献类型：
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作者：
Isogai, E;Isogai, H;Takeshi, K
用肠出血性大肠杆菌（EHEC）O 157：H7菌株接种的无菌小鼠出现弛缓性轻瘫，通常最终死亡。细菌以10（9）至10（10）CFU/g（接种量：2.0 x 10（9）CFU/小鼠）定植于粪便中，并在粪便中检测到志贺样毒素（SLT）。结肠显微镜检查显示轻度炎性细胞浸润、肠壁变薄或坏死灶。在这些有症状的小鼠中观察到肾小管细胞坏死，还观察到脑的微出血、血栓形成和水肿变化，炎性细胞因子、肿瘤坏死因子α（TNF-α）、白细胞介素1 α在EHEC感染后的肾脏中检测到IL-1 α和IL-6，而在血清中未检测到，在脑中仅检测到TNF-α，当用2.0 × 10（2）CFU的EHEC O 157：H7喂养无菌小鼠时，细菌数量在第1天开始迅速上升，并维持在10（8）至10（9）CFU/g粪便，在小鼠粪便中仅检测到SLTs。然而，小鼠没有表现出与对照组相似的组织学变化和细胞因子反应。用TNF-α治疗的小鼠出现严重的神经毒性症状，并具有更高频率的全身症状和肾小球病理学。在肾和脑中观察到强烈的细胞因子应答，同时检测血清细胞因子水平。相反，TNF-α抑制剂（蛋白酶抑制剂）抑制这些反应，特别是在脑中。然而，在肾脏中观察到细胞因子的局部合成。因此，TNF-α和其他促炎细胞因子在改善由EHEC引起的疾病中可能是重要的。
Gnotobiotic mice inoculated with an enterohemorrhagic Escherichia coli (EHEC) O157:H7 strain developed a flaccid paresis, usually culminating in death. The bacteria colonized feces at 10(9) to 10(10) CFU per g (inoculum size: 2.0 x 10(9) CFU/mouse), and Shiga-like toxins (SLTs) were detected in the feces, A microscopic examination of colons showed mild inflammatory cell infiltration, thinning of the intestinal wall, or necrotic foci. Necrosis of tubular cells was noted in these symptomatic mice, Microhemorrhage, thrombosis, and edematous changes of the brain were also seen, Inflammatory cytokines, tumor necrosis factor alpha (TNF-alpha), interleukin 1 alpha (IL-1 alpha), and IL-6, were detected in the kidney after EHEC infection, but not in the serum, In the brain, only TNF-or was detected, When 2.0 x 10(2) CFU of EHEC O157:H7 was fed to germ-free mice, the number of bacteria began to rise rapidly on day I and was maintained at 10(8) to 10(9) CFU/g of feces, SLTs mere detected in the feces of the mice, However, the mice showed no histological changes and no cytokine responses, similar to what was found for controls, Treatment with TNF-alpha modified the clinical neural signs, histopathological changes, and cytokine responses; mice treated,vith TNF-alpha developed severe neurotoxic symptoms and had higher frequencies of systemic symptoms and glomerular pathology, Strong cytokine responses were seen in the kidney and brain, Serum cytokines were also detected in this group. In contrast, a TNF-alpha inhibitor (protease inhibitor) inhibited these responses, especially in the brain, However, local synthesis of the cytokines was observed in the kidney, Thus, TNF-or and the other proinflammatory cytokines could be important in modifying the disease caused by EHEC.