Shankar G, Scott Bryson J, Darrell Jennings C, Kaplan A M, Cohen D A
Department of Microbiology, University of Kentucky Chandler Medical Center, Lexington, Kentucky 40536-0084, USA.
Am J Respir Cell Mol Biol. 1999 Jun;20(6):1116-24. doi: 10.1165/ajrcmb.20.6.3455.
Idiopathic pneumonia syndrome (IPS) is a significant clinical problem encountered among patients treated with bone marrow transplantation (BMT). IPS is identified as an inflammatory lung disease characterized by diffuse interstitial pneumonitis and alveolitis leading to interstitial fibrosis in the absence of an identifiable infectious agent. In an earlier study we characterized a murine model of IPS following allogeneic BMT that exhibits several features of human IPS. In this report we show that the lung represents a unique target of post-BMT disease in this model. The kinetics of developing lung disease were found to be markedly different from the kinetics of graft-versus-host disease in other tissues such as liver, colon, ear, skin, and tongue. Mice transplanted by our standard protocol with T-cell-depleted semiallogeneic donor bone marrow plus donor spleen cells in the absence of pretransplant radiation conditioning did not develop lung inflammation or fibrosis characteristic of IPS. Pretransplant radiation conditioning in the absence of BMT also failed to cause IPS, demonstrating an important role for radiation conditioning in the development of BMT-related IPS. The occurrence of lung disease post-BMT was found to be dependent on radiation conditioning in a dose-dependent manner. Finally, thoracic irradiation alone was demonstrated to be sufficient in causing IPS in mice transplanted with bone marrow plus spleen cells, albeit with reduced severity. Based on these findings, we conclude that pretransplant radiation conditioning plays an important role in the development of IPS following allogeneic BMT.
特发性肺炎综合征（IPS）是接受骨髓移植（BMT）的患者中遇到的一个重要临床问题。IPS被确定为一种炎症性肺部疾病，其特征为弥漫性间质性肺炎和肺泡炎，最终导致间质纤维化，且不存在可识别的感染因子。在早期的一项研究中，我们对异基因BMT后的IPS小鼠模型进行了表征，该模型展现出人类IPS的若干特征。在本报告中，我们表明在该模型中，肺是BMT后疾病的一个独特靶点。发现肺部疾病的发展动力学与其他组织（如肝脏、结肠、耳朵、皮肤和舌头）中移植物抗宿主病的动力学明显不同。按照我们的标准方案，在没有移植前放疗预处理的情况下，用T细胞去除的半同种异体供体骨髓加供体脾细胞移植的小鼠未出现IPS特征性的肺部炎症或纤维化。在没有BMT的情况下进行移植前放疗预处理也未能引发IPS，这表明放疗预处理在与BMT相关的IPS发展中起重要作用。发现BMT后肺部疾病的发生以剂量依赖的方式取决于放疗预处理。最后，单独的胸部照射被证明足以在接受骨髓加脾细胞移植的小鼠中引发IPS，尽管严重程度有所降低。基于这些发现，我们得出结论，移植前放疗预处理在异基因BMT后IPS的发展中起重要作用。
