Differential host inflammatory responses to viable versus antibiotic-killed bacteria in experimental microbial sepsis.
Differential host inflammatory responses to viable versus antibiotic-killed bacteria in experimental microbial sepsis.
复制标题
在实验性微生物败血症中，宿主对活细菌和抗生素杀死细菌的不同炎症反应。
DOI：
10.1128/iai.68.4.2301-2308.2000
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发表时间：
2000
影响因子：
3.1
通讯作者：
Morrison,DC
中科院分区：
文献类型：
--
作者：
Silverstein,R;Wood,JG;Xue,Q;Norimatsu,M;Horn,DL;Morrison,DC
在亚胺培南或头孢他啶化疗期间杀死的小鼠金黄色葡萄球菌引起肿瘤坏死因子α（TNF-α）早期释放到体循环中。这种反应与微血管中白细胞-内皮细胞粘附相互作用的增加在时间上是一致的。在未使用抗生素治疗（亚胺培南或头孢他啶）的情况下，未观察到等效反应。与对照组相比，相同抗生素治疗的保护功效显著降低了吲哚-半乳糖胺治疗的小鼠;例如，在攻毒时给予每公斤4毫克亚胺培南，它从2，000倍下降到70倍。然而，对这些TNF-α超敏小鼠同时给予中和抗TNF-α抗体或4 mg地塞米松/kg后，保护作用定量恢复。重要的是，当动物用活微生物攻毒但不同时给予抗生素时，未观察到地塞米松提供的保护。用大肠杆菌激发后也可显示早期TNF-α应答，但在这种情况下，这些抗生素治疗对应答的时间和幅度均无影响。我们从这些研究中得出结论，对活菌和灭活菌的炎症反应可能因特定细菌、宿主对TNF-α的敏感性以及革兰氏染色分类而显著不同。
Staphylococcus aureuskilled during imipenem or ceftazidime chemotherapy in mice elicited an early release of tumor necrosis factor alpha (TNF-α) into the systemic circulation. This response was coincident in time with an increase in leukocyte-endothelium adhesive interactions in the microvasculature. Equivalent responses were not observed without the antibiotic treatment (imipenem or ceftazidime). Protective efficacy of the same antibiotic treatment was markedly diminished ind-galactosamine-treated mice compared to controls; e.g., it dropped from 2,000-fold to 70-fold with 4 mg of imipenem per kg given at the time of challenge. Nevertheless, protection was quantitatively restored upon concurrent administration of neutralizing anti-TNF-α antibody or 4 mg of dexamethasone per kg to these TNF-α-hypersensitive mice. Importantly, protection afforded by dexamethasone was not seen when the animals were challenged with viable organisms but without the concurrent administration of antibiotic. An early TNF-α response could also be demonstrated upon challenge withEscherichia coli, but in this instance, neither the timing nor the magnitude of that response was influenced by treatment with these antibiotics. We conclude from these studies that the inflammatory response to viable versus killed bacteria may differ markedly depending on the particular bacterium, host sensitivity to TNF-α, and possibly the Gram stain classification.