Gu Y, Takao M, Kai M, Lu L, Shimamoto A, Onoda K, Shimono T, Tanaka K, Shimpo H, Shiraishi T, Yada I
Department of Thoracic and Cardiovascular Surgery, School of Medicine, Mie University, 2-174 Edobashi, Tsu, Mie 514-8507, Japan.
Ann Thorac Cardiovasc Surg. 2000 Aug;6(4):224-31.
The pathogenesis of obliterative bronchiolitis (OB) following lung and heart-lung transplantation remains unclear. We evaluated the role of CsA and IL-2 on the development of obliterative airway disease (OAD) by administrating exogenous IL-2 in a CsA-treated rat tracheal transplant model. Tracheal grafts were implanted into the peritoneal cavity from Brown Norway (BN) to BN rats or to Lewis (LEW) rats. Allotransplant: No treatment was given in group 1. Short-term CsA (25 mg/kg, i.m. on POD 2 and 3) was used in group 2. Group 3 was treated with long-term CsA (25 mg/kg, i.m. on POD 2 and 3, followed by 5 mg/kg on POD 4 to 27). Administration of IL-2 (300, 000 IU/kg, i.p. on POD 15 to 19 and 22 to 26) was performed to long-term CsA treated rats in group 4. Isotransplant: No treatment was given to group 5, group 6 was treated with IL-2 (same regimen as in group 4). Grafts were harvested at different time points after Tx for histological assessment. No luminal obliteration was observed in group 5 and 6. Complete luminal obliteration was noted 4 weeks after Tx in group 1. In group 2 and 3, obliterative lesion occurred 4-6 weeks after CsA withdrawal. IL-2 increased epithelial loss, lymphocytic infiltration, and obliterative changes in group 4. Our results suggest that OAD is an immune mediated disorder. Furthermore, administration of exogenous IL-2 might be able to abrogate the protection from OAD by CsA therapy.
肺移植和心肺移植后闭塞性细支气管炎（OB）的发病机制尚不清楚。我们通过在环孢素（CsA）处理的大鼠气管移植模型中给予外源性白细胞介素-2（IL-2），评估了CsA和IL-2在闭塞性气道疾病（OAD）发生发展中的作用。将气管移植物从棕色挪威大鼠（BN）植入到BN大鼠或刘易斯大鼠（LEW）的腹腔内。同种异体移植：第1组不进行任何处理。第2组使用短期CsA（25mg/kg，在术后第2天和第3天肌肉注射）。第3组使用长期CsA（25mg/kg，在术后第2天和第3天肌肉注射，随后在术后第4天至第27天给予5mg/kg）。对第4组长期接受CsA治疗的大鼠给予IL-2（300,000IU/kg，在术后第15天至第19天以及第22天至第26天腹腔注射）。同基因移植：第5组不进行任何处理，第6组给予IL-2（给药方案与第4组相同）。在移植术后不同时间点采集移植物进行组织学评估。第5组和第6组未观察到管腔闭塞。第1组在移植术后4周出现完全管腔闭塞。在第2组和第3组，CsA撤药后4 - 6周出现闭塞性病变。IL-2增加了第4组的上皮细胞丢失、淋巴细胞浸润和闭塞性改变。我们的结果表明，OAD是一种免疫介导的疾病。此外，给予外源性IL-2可能会消除CsA治疗对OAD的保护作用。
