Cigarette smoking has been implicated in the pathogenesis of seropositive rheumatoid arthritis (RA), as well as RA-associated lung disease. Fibrotic interstitial lung disease as well as emphysema occur in RA and cause substantial morbidity. We used arthritis-susceptible HLA-DQ8 transgenic mice to generate RA-associated lung disease. Mice were exposed to cigarette smoke (CS) prior to induction of arthritis, and subsequently injected with a low dose of bleomycin intra-tracheally to induce lung injury. Exposure of arthritic mice to both CS and bleomycin led to a significant reduction in lung compliance consistent with development of diffuse lung disease. Morphologic evaluation of the lung demonstrated areas of emphysematous change and co-existent fibrosis, consistent with a combined pattern of fibrosis and emphysema. These changes were accompanied by inflammatory cell infiltration and upregulation of fibrosis-associated genes. This humanized mouse model can serve as a valuable research tool to understand the pathogenesis of RA associated lung disease.

吸烟与血清阳性类风湿性关节炎 (RA) 以及 RA 相关肺病的发病机制有关。纤维化间质性肺病以及肺气肿发生在 RA 中并导致大量发病率。我们使用关节炎易感的 HLA-DQ8 转基因小鼠来产生 RA 相关的肺病。小鼠在诱发关节炎之前暴露于香烟烟雾 (CS) 中，随后在气管内注射低剂量的博莱霉素以诱发肺损伤。关节炎小鼠暴露于 CS 和博莱霉素导致肺顺应性显着降低，与弥漫性肺病的发展一致。肺的形态学评估显示肺气肿改变和共存的纤维化区域，与纤维化和肺气肿的组合模式一致。这些变化伴随着炎症细胞浸润和纤维化相关基因的上调。这种人源化小鼠模型可以作为了解 RA 相关肺病发病机制的宝贵研究工具。