Duong M, Ouellet N, Simard M, Bergeron Y, Olivier M, Bergeron M G
Centre de Recherche en Infectiologie, Centre Hospitalier de l'UniversitéLaval, Sainte-Foy, Canada.
J Infect Dis. 1998 Nov;178(5):1472-82. doi: 10.1086/314425.
The sequential pathogenesis of pulmonary aspergillosis was studied and the role of inflammatory cytokines in host response to Aspergillus fumigatus was characterized in immunocompetent and immunosuppressed mice. Two distinct phases were observed in immunocompetent mice: First, an intense clearance of A. fumigatus occurred, possibly through alveolar macrophages and recruited neutrophils (PMNL), accompanied by rapid release of tumor necrosis factor-alpha, interleukin (IL)-6, and IL-1beta, and second, cellular and fungal debris were cleaned by recruited monocytes, cytokine production rapidly decreased, and pneumonia self-healed. In contrast, cortisone-treated animals had, first, an altered clearance of conidia and delayed cytokine production and inflammatory cell recruitment; second, an invasive process in lungs, recruitment of PMNL, and release of IL-6 and IL-1beta; and third, widespread tissue necrosis, sustained release of IL-6 and IL-1beta, further increases in PMNL trafficking but no monocyte recruitment, respiratory failure, and 100% mortality within 5 days. These insights may be useful in the development of new treatment strategies for pulmonary aspergillosis.
研究了肺曲霉病的序贯发病机制，并在免疫功能正常和免疫抑制的小鼠中，对炎性细胞因子在宿主对烟曲霉反应中的作用进行了表征。在免疫功能正常的小鼠中观察到两个不同阶段：第一，烟曲霉被强烈清除，可能是通过肺泡巨噬细胞和募集的中性粒细胞（PMNL），同时肿瘤坏死因子-α、白细胞介素（IL）-6和IL-1β迅速释放；第二，募集的单核细胞清除细胞和真菌碎片，细胞因子产生迅速减少，肺炎自愈。相比之下，经可的松治疗的动物首先出现分生孢子清除改变、细胞因子产生延迟和炎性细胞募集延迟；其次是肺部的侵袭过程、PMNL募集以及IL-6和IL-1β释放；第三是广泛的组织坏死、IL-6和IL-1β持续释放、PMNL迁移进一步增加但无单核细胞募集、呼吸衰竭以及5天内100%死亡。这些见解可能有助于开发肺曲霉病的新治疗策略。
