Brieland J K, Remick D G, Freeman P T, Hurley M C, Fantone J C, Engleberg N C
Unit for Laboratory Animal Medicine, University of Michigan, Ann Arbor 48109-0614, USA.
Infect Immun. 1995 Sep;63(9):3253-8. doi: 10.1128/iai.63.9.3253-3258.1995.
The in vivo role of endogenous tumor necrosis factor alpha (TNF-alpha) and reactive nitrogen intermediates (RNIs) in modulation of growth of Legionella pneumophila in the lung was assessed using a murine model of replicative L. pneumophila lung infection. Intratracheal inoculation of mice with L. pneumophila resulted in induction of endogenous TNF-alpha, which preceded clearance of L. pneumophila from the lung. Inhibition of endogenous TNF-alpha activity, via in vivo administration of TNF-alpha neutralizing antibody, or inhibition of endogenous RNIs, via administration of the nitric oxide (NO) synthetase inhibitor N-monomethyl-L-arginine (NMMA), resulted in enhanced growth of L. pneumophila in the lung at > or = 3 days postinfection (when compared with untreated L. pneumophila-infected mice). Because of the similar kinetics of enhanced pulmonary growth of L. pneumophila in mice treated in vivo with either anti-TNF-alpha antibody or NMMA, the immunomodulatory effect of NO on endogenous TNF-alpha activity in the lung was assessed. Administration of NMMA to L. pneumophila-infected mice resulted in a significant decrease in endogenous TNF-alpha activity in the lung during replicative L. pneumophila infections in vivo. However, administration of exogenous TNF-alpha to NMMA-treated mice failed to significantly enhance clearance of L. pneumophila from the lung. Results of these studies indicate that both endogenous NO and TNF-alpha facilitate resolution of replicative L. pneumophila lung infections and that regulation of L. pneumophila replication by TNF-alpha is mediated, at least in part, by NO.
利用嗜肺军团菌肺部复制感染的小鼠模型，评估内源性肿瘤坏死因子α（TNF-α）和活性氮中间体（RNI）在调节肺部嗜肺军团菌生长中的体内作用。给小鼠气管内接种嗜肺军团菌可诱导内源性TNF-α产生，这发生在嗜肺军团菌从肺部清除之前。通过体内给予TNF-α中和抗体抑制内源性TNF-α活性，或通过给予一氧化氮（NO）合酶抑制剂N-单甲基-L-精氨酸（NMMA）抑制内源性RNI，导致感染后≥3天时肺部嗜肺军团菌生长增强（与未治疗的嗜肺军团菌感染小鼠相比）。由于用抗TNF-α抗体或NMMA体内治疗的小鼠中嗜肺军团菌肺部生长增强的动力学相似，因此评估了NO对肺部内源性TNF-α活性的免疫调节作用。在嗜肺军团菌体内复制感染期间，给感染嗜肺军团菌的小鼠施用NMMA导致肺部内源性TNF-α活性显著降低。然而，给NMMA治疗的小鼠施用外源性TNF-α未能显著增强嗜肺军团菌从肺部的清除。这些研究结果表明，内源性NO和TNF-α都有助于解决嗜肺军团菌肺部复制感染，并且TNF-α对嗜肺军团菌复制的调节至少部分是由NO介导的。
