Skerrett S J, Bagby G J, Schmidt R A, Nelson S
Department of Veterans Affairs Puget Sound Health Care System, and Department of Medicine, University of Washington School of Medicine, Seattle 98108, USA.
J Infect Dis. 1997 Oct;176(4):1019-28. doi: 10.1086/516530.
Tumor necrosis factor-alpha (TNF-alpha) has been shown to stimulate the resistance of alveolar macrophages and neutrophils to Legionella pneumophila in vitro. To determine whether endogenous TNF-alpha is necessary for host defense against legionellosis in vivo, anti-TNF-alpha IgG or control IgG was administered to rats exposed to aerosolized L. pneumophila. Treatment with anti-TNF-alpha neutralized >90% of the intrapulmonary TNF-alpha response to infection, resulting in persistent pneumonitis and failure to clear L. pneumophila from the lungs. Depletion of TNF-alpha limited the recruitment of mononuclear cells to the lungs and resulted in a progressive increase in the proportion of alveolar macrophages that were infected; neutrophil recruitment and phagocytosis were not impaired. Both systemic and intrapulmonary IFN-gamma levels were significantly higher in rats depleted of TNF-alpha. These observations indicate that TNF-alpha is required for the prompt resolution of pneumonic legionellosis and point to a direct role for TNF-alpha in the activation of phagocytes.
肿瘤坏死因子-α（TNF-α）已被证明在体外可刺激肺泡巨噬细胞和中性粒细胞对嗜肺军团菌的抵抗力。为了确定内源性TNF-α在体内对军团菌病宿主防御是否必要，将抗TNF-α IgG或对照IgG给予暴露于雾化嗜肺军团菌的大鼠。用抗TNF-α治疗可中和>90%的肺部对感染的TNF-α反应，导致持续性肺炎且无法从肺部清除嗜肺军团菌。TNF-α的耗竭限制了单核细胞向肺部的募集，并导致被感染的肺泡巨噬细胞比例逐渐增加；中性粒细胞的募集和吞噬作用未受损。TNF-α耗竭的大鼠全身和肺内IFN-γ水平均显著升高。这些观察结果表明，TNF-α是肺炎型军团菌病迅速消退所必需的，并表明TNF-α在吞噬细胞激活中起直接作用。
