Molecular characterization of the acute inflammatory response to infections with gram-negative versus gram-positive bacteria
Molecular characterization of the acute inflammatory response to infections with gram-negative versus gram-positive bacteria
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DOI：
10.1128/iai.71.10.5803-5813.2003
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发表时间：
2003-10-01
影响因子：
3.1
通讯作者：
Oberholzer, A
中科院分区：
文献类型：
--
作者：
Feezor, RJ;Oberholzer, C;Oberholzer, A
革兰氏阴性菌引起的败血症与革兰氏阳性菌引起的败血症往往表现出相似的临床特征。我们研究了革兰氏阳性和革兰氏阴性细菌引起的脓毒症患者血浆促炎细胞因子谱，并研究了大肠杆菌脂多糖或热杀金黄色葡萄球菌体外刺激白细胞的细胞因子产生和差异基因调控。患者血浆中肿瘤坏死因子α、白细胞介素I受体拮抗剂（IL-1Ra）、IL-8、IL-10、IL-18结合蛋白、降钙素原和蛋白C的浓度在革兰氏阴性菌和革兰氏阳性菌引起的败血症中没有差异。然而，革兰氏阳性菌引起的败血症患者血浆il -1 β、IL-6和IL-18浓度明显升高。体外热杀金黄色葡萄球菌刺激全血，il -1 β和IL-18水平明显高于大肠杆菌脂多糖刺激。微阵列分析显示，至少有359个交叉验证的探针组（基因）在P < 0.001水平上显著，其表达在革兰氏阴性生物刺激、革兰氏阳性生物刺激和未刺激的全血白细胞中有区别。宿主对革兰氏阴性和革兰氏阳性刺激的炎症反应有一些共同的反应要素，但也表现出不同的细胞因子外观和白细胞基因表达模式。
Sepsis caused by gram-negative bacteria and that caused by gram-positive bacteria often manifest similar clinical features. We investigated plasma proinflammatory cytokine profiles in patients with sepsis due to gram-positive and gram-negative bacteria and studied the cytokine production and differential gene regulation of leukocytes stimulated ex vivo with Escherichia coli lipopolysaccharide or heat-killed Staphylococcus aureus. Concentrations of tumor necrosis factor alpha, interleukin I receptor antagonist (IL-1Ra), IL-8, IL-10, IL-18 binding protein, procalcitonin, and protein C in plasma did not differ between patients with sepsis due to gram-negative and gram-positive bacteria. However, plasma IL-1beta, IL-6, and IL-18 concentrations were significantly higher in patients with sepsis due to gram-positive bacteria. Ex vivo stimulation of whole blood with heat-killed S. aureus markedly increased IL-1beta and IL-18 levels more than E. coli lipopolysaccharide stimulation. Microarray analysis revealed at least 359 cross-validated probe sets (genes) significant at the P < 0.001 level whose expression discriminated among gram-negative-organism-stimulated, gram-positive-organism-stimulated, and unstimulated whole-blood leukocytes. The host inflammatory responses to gram-negative and gram-positive stimuli share some common response elements but also exhibit distinct patterns of cytokine appearance and leukocyte gene expression.