Passive immunization against tumor necrosis factor-alpha impairs host defense during pneumococcal pneumonia in mice.
Passive immunization against tumor necrosis factor-alpha impairs host defense during pneumococcal pneumonia in mice.
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DOI：
10.1164/ajrccm.155.2.9032201
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发表时间：
1997-02
影响因子：
24.7
通讯作者：
T. Poll;C. Keogh;W. Buurman;S. Lowry
中科院分区：
文献类型：
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作者：
T. Poll;C. Keogh;W. Buurman;S. Lowry
肺炎链球菌是社区获得性肺炎最常见的原因。我们试图确定肿瘤坏死因子-α（TNF）在肺炎球菌性肺炎发病机制中的作用。通过鼻内接种10（6）个菌落形成单位（cfu）S诱导C57 B1/6小鼠肺炎。肺炎克雷伯氏菌导致肺匀浆中TNF活性持续增加，在12和72小时之间达到平台（72小时：185.49 +/- 54.41 ng/g），而血浆TNF活性保持较低或检测不到。接种前2小时用中和性抗TNF单克隆抗体治疗可显著降低肺TNF活性，但仅适度降低肺白细胞介素（IL）-1 β水平，对肺IL-6、IL-10和干扰素-γ浓度无显著影响。抗肿瘤坏死因子治疗的小鼠有四倍多的S。在接种后40小时，从肺分离的肺炎克雷伯氏菌cfu的活性高于对照小鼠（P < 0.05），尽管两个治疗组中肺髓过氧化物酶活性相似。抗TNF处理的小鼠比对照小鼠显著更早死于肺炎球菌肺炎（p < 0.05）。内源性产生的TNF在肺炎球菌肺炎中对宿主防御很重要。
Streptococcus pneumoniae is the most frequent cause of community-acquired pneumonia. We sought to determine the role of tumor necrosis factor-alpha (TNF) in the pathogenesis of pneumococcal pneumonia. Induction of pneumonia in C57B1/6 mice by intranasal inoculation with 10(6) colony-forming units (cfu) S. pneumoniae resulted in a sustained increase in TNF activity in lung homogenates reaching a plateau between 12 and 72 h (72 h: 185.49 +/- 54.41 ng/g), while plasma TNF activity remained low or undetectable. Treatment with a neutralizing anti-TNF monoclonal antibody 2 h before inoculation strongly reduced lung TNF activity, but only modestly diminished lung interleukin (IL)-1beta levels, and did not significantly influence lung IL-6, IL-10, and interferon-gamma concentrations. Anti-TNF-treated mice had fourfold more S. pneumoniae cfu isolated from lungs than control mice 40 h after inoculation (p < 0.05), although lung myeloperoxidase activities were similar in both treatment groups. Anti-TNF-treated mice died significantly earlier from pneumococcal pneumonia than control mice (p < 0.05). Endogenously produced TNF is important for host defense during pneumococcal pneumonia.