Dallaire F, Ouellet N, Bergeron Y, Turmel V, Gauthier M C, Simard M, Bergeron M G
Centre de Recherche en Infectiologie, Université Laval, Québec City, Québec, Canada.
J Infect Dis. 2001 Aug 1;184(3):292-300. doi: 10.1086/322021. Epub 2001 Jun 26.
Pneumococcal pneumonia still is associated with a high mortality rate, despite appropriate antimicrobial therapy. Many gaps remain in the understanding of the pathogenesis of this deadly infection. The microbial and inflammatory events that characterize survival or death after intranasal inoculation of mice with an LD(50) inoculum of Streptococcus pneumoniae were investigated. Survival was associated with rapid bacterial clearance and low inflammation (surfactant and red blood cells in alveoli), but no neutrophil recruitment or lung tissue injury was noted. By contrast, death was preceded by strong bacterial growth that peaked 48 h after the infection and was associated with gradual increases in pulmonary levels of interleukin-6, macrophage inflammatory protein (MIP)-1alpha, MIP-2, monocyte chemoattractant protein-1, KC, and neutrophil recruitment. The injection of tumor necrosis factor-alpha or the addition of lipopolysaccharide or heat-killed S. pneumoniae to the inoculum enhanced early host response and survival. These observations may help develop appropriate markers of evolution of pneumonia, as well as new therapeutic strategies.
尽管采用了适当的抗菌治疗，但肺炎球菌肺炎的死亡率仍然很高。在对这种致命感染的发病机制的理解方面仍存在许多空白。我们研究了用肺炎链球菌半数致死剂量（LD50）接种物经鼻接种小鼠后，表征存活或死亡的微生物和炎症事件。存活与细菌的快速清除和低炎症反应（肺泡中的表面活性剂和红细胞）相关，但未观察到中性粒细胞募集或肺组织损伤。相比之下，死亡之前细菌大量繁殖，在感染后48小时达到峰值，并与肺中白细胞介素-6、巨噬细胞炎性蛋白（MIP）-1α、MIP-2、单核细胞趋化蛋白-1、KC水平的逐渐升高以及中性粒细胞募集相关。注射肿瘤坏死因子-α或在接种物中添加脂多糖或热灭活的肺炎链球菌可增强早期宿主反应并提高存活率。这些观察结果可能有助于开发肺炎病情演变的合适标志物以及新的治疗策略。
