Streptococcus pneumoniae and Pseudomonas aeruginosa pneumonia induce distinct host responses
Streptococcus pneumoniae and Pseudomonas aeruginosa pneumonia induce distinct host responses
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DOI：
10.1097/ccm.0b013e3181b4a76b
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发表时间：
2010-01-01
影响因子：
8.8
通讯作者：
Coppersmith, Craig M.
中科院分区：
文献类型：
--
作者：
McConnell, Kevin W.;McDunn, Jonathan E.;Coppersmith, Craig M.
目的：引起肺炎的病原体可以通过抗生素以靶向方式治疗，但如果这种治疗失败，那么治疗仅涉及非特异性支持措施，与煽动感染无关。本研究的目的是确定宿主反应是否相似后，不同的感染与相似的mortification.Design：前瞻性，随机对照study.Setting：动物实验室在一所大学的医疗中心。在FVB/N小鼠中通过肺炎链球菌或两种不同浓度的铜绿假单胞菌诱导肺炎。血浆和支气管肺泡灌洗液脓毒症动物进行了测定，通过微阵列免疫测定法测量18炎症介质在多个时间points.Measurements和主要结果：宿主反应是依赖于致病生物体以及动力学的死亡率，但促炎和抗炎反应是独立的接种浓度或菌血症的程度。由不同浓度的相同细菌铜绿假单胞菌引起的肺炎也产生了不同的炎症反应;然而，炎症介质表达并不直接追踪感染的严重程度。对于所有感染，宿主反应是区室化的，在体循环和肺中具有显著不同的炎症介质浓度。层次聚类分析导致五个不同的集群的主机响应细菌感染的鉴定。主成分分析相关的肺巨噬细胞炎性肽-2和白细胞介素-10与感染的进展，而升高的血浆肿瘤坏死因子SR 2和巨噬细胞趋化肽-1的暴发性疾病与>90%的死亡率在48 hrs.Conclusions：脓毒症小鼠有不同的局部和全身反应肺炎链球菌和铜绿假单胞菌肺炎。靶向由不同细菌感染诱导的特异性宿主炎症反应可能代表治疗脓毒症的潜在治疗方法。(Crit Care Med 2010; 38：223-241）
Objective: Pathogens that cause pneumonia may be treated in a targeted fashion by antibiotics, but if this therapy fails, then treatment involves only nonspecific supportive measures, independent of the inciting infection. The purpose of this study was to determine whether host response is similar after disparate infections with similar mortalities.Design: Prospective, randomized controlled study.Setting: Animal laboratory in a university medical center.Interventions. Pneumonia was induced in FVB/N mice by either Streptococcus pneumoniae or two different concentrations of Pseudomonas aeruginosa. Plasma and bronchoalveolar lavage fluid from septic animals was assayed by a microarray immunoassay measuring 18 inflammatory mediators at multiple time points.Measurements and Main Results: The host response was dependent on the causative organism as well as kinetics of mortality, but the pro-inflammatory and anti-inflammatory responses were independent of inoculum concentration or degree of bacteremia. Pneumonia caused by different concentrations of the same bacteria, Pseudomonas aeruginosa, also yielded distinct inflammatory responses; however, inflammatory mediator expression did not directly track the severity of infection. For all infections, the host response was compartmentalized, with markedly different concentrations of inflammatory mediators in the systemic circulation and the lungs. Hierarchical clustering analysis resulted in the identification of five distinct clusters of the host response to bacterial infection. Principal components analysis correlated pulmonary macrophage inflammatory peptide-2 and interleukin-10 with progression of infection, whereas elevated plasma tumor necrosis factor sr2 and macrophage chemotactic peptide-1 were indicative of fulminant disease with >90% mortality within 48 hrs.Conclusions: Septic mice have distinct local and systemic responses to Streptococcus pneumoniae and Pseudomonas aeruginosa pneumonia. Targeting specific host inflammatory responses induced by distinct bacterial infections could represent a potential therapeutic approach in the treatment of sepsis. (Crit Care Med 2010; 38:223-241)