Tumor necrosis factor mediates lung antibacterial host defense in murine Klebsiella pneumonia
Tumor necrosis factor mediates lung antibacterial host defense in murine Klebsiella pneumonia
复制标题
DOI：
10.1128/iai.64.12.5211-5218.1996
复制
发表时间：
1996-12-01
影响因子：
3.1
通讯作者：
Standiford, TJ
中科院分区：
文献类型：
--
作者：
Laichalk, LL;Kunkel, SL;Standiford, TJ
肿瘤坏死因子（TNF）是一种促炎细胞因子，最近已被证明对获得性宿主免疫有有益的作用，然而，TNF在先天性免疫应答中的作用，如在细菌性肺炎的情况下，尚未完全表征。为了确定TNF在革兰氏阴性细菌性肺炎中的作用，CBA/J小鼠气管内注射了10(2)CFU的肺炎克雷伯菌，导致肺内TNF MRNA和蛋白的时间依赖性表达，在肺炎克雷伯菌接种前2小时腹腔被动免疫可溶性TNF受体-免疫球蛋白（sTNFR:Fc）的动物，与接受对照IgG1的动物相比，在48小时内，支气管肺泡灌胃中性粒细胞显著减少，但巨噬细胞没有显著减少。与对照组IgG1相比，sTNFR:Fc治疗导致肺匀浆和血浆中肺炎克雷伯菌CFU分别增加19.6倍和13.5倍。最后，用sTNFR:Fc治疗克雷伯菌感染小鼠显着降低了这些动物的短期和长期生存率。总之，我们的研究表明，内源性TNF是小鼠肺炎克雷伯菌抗菌宿主防御的关键组成部分。
Tumor necrosis factor (TNF) is a proinflammatory cytokine which has recently been shown to have beneficial effects in the setting of acquired host immunity, However, the role of TNF in innate immune responses, as in the setting of bacterial pneumonia, has been incompletely characterized, To determine the role of TNF in gram-negative bacterial pneumonia, CBA/J mice were challenged with 10(2) CFU of Klebsiella pneumoniae intratracheally, resulting in the time-dependent expression of TNF MRNA and protein within the lung, Passive immunization of animals with a soluble TNF receptor-immunoglobulin (Ig) construct (sTNFR:Fc) intraperitoneally 2 h prior to K. pneumoniae inoculation resulted in a significant reduction in bronchoalveolar lavage neutrophils, but not macrophages, at 48 h, as compared with animals receiving control IgG1, Furthermore, treatment with sTNFR:Fc resulted in 19.6- and 13.5-fold increases in K. pneumoniae CFU in lung homogenates and plasma, respectively, as compared with animals receiving control IgG1, Finally, treatment of Klebsiella-infected mice with sTNFR:Fc markedly decreased both short- and long-term survival of these animals. In conclusion, our studies indicate that endogenous TNF is a critical component of antibacterial host defense in murine Klebsiella pneumonia.