Interleukin-10 Gene Transfer to The Airway of Rat Lungs for Prevention of Lung Allograft Rejection

背景：表达具有潜在免疫调节能力的基因的能力可以减少同种异体移植排斥反应（AR）。我们研究了通过支气管内滴注将il -10基因转入大鼠肺的可行性，以及随后传递的il -10对急性肺部AR的影响。方法：首先，将腺病毒β-半乳糖苷酶载体（adv-β-gal）颗粒滴入大鼠肺，通过组织化学染色证实β-gal蛋白的合成。接下来，在高度组织不相容的大鼠肺移植模型（BN→Lew）中检测腺病毒vIL-10载体（adv-vIL-10）转染修饰AR的能力。在移植前3天用3 × 10^8 pfu/0.3mL adv- vil -10或adv-β-gal转染供体左肺。移植后第6天，对AR进行组织学分级（0-4期）。炎症的几个病理类别也按0-4分进行评分。结果：adv- vil -10组AR分期为3.75±0.5，adv-β-gal组AR分期为4.0±0，差异无统计学意义。水肿程度（3.5±0.6 vs. 4±0）、血管炎程度（1.5±0.6 vs. 1.5±0.6）、坏死程度（1.5±0.5 vs. 1.75±1.3）、出血程度（2.3±1.0 vs. 2.5±0.6）均无显著差异。结论：本初步研究表明，转染adv-vIL-10似乎并没有显著降低肺AR，这与我们之前在大鼠心脏移植模型中的实验结果相反。这种差异可能是由腺病毒载体的免疫原性解释的，脂质体介导的IL-10递送减少肺AR的能力目前正在研究中。

Background : The ability to express genes with potential immunoregulatory capacity could reduce allograft rejection (AR). We examined the feasibility of transferring the vIL-10 gene into rat lungs by intra-bronchial instillation and the subsequent effects of delivered vIL-10 on acute lung AR. Methods : First, the adenoviral β-galactosidase vector (adv-β-gal) particles were instilled into the rat lung and protein synthesis of β-gal was confirmed by histochemical staining. Next, the ability of the adenoviral vIL-10 vector (adv-vIL-10) transfection to modify AR was examined in a highly histoincompatible rat lung transplant model (BN→Lew). Donor left lungs were transfected with 3x10^8 pfu/0.3mL of adv-vIL-10 or adv-β-gal 3 days before transplantation. On day 6 post-transplant, AR was graded histologically (stage 0-4). Several pathological categories of inflammation were also scored on a scale of 0-4. Results : The stage of AR was 3.75±0.5 in the adv-vIL-10 group and 4.0±0 in the adv-β-gal group, and the difference did not reach a statistically significant difference. There were no significant differences either in the degree of edema (3.5±0.6 vs. 4±0), vasculitis (1.5±0.6 vs. 1.5±0.6), necrosis (1.5±0.5 vs. 1.75±1.3), and hemorrhage (2.3±1.0 vs. 2.5±0.6). Conclusion : This preliminary study showed that transfection of adv-vIL-10 did not seem to reduce lung AR significantly, as opposed to the results of our previous experiments in a rat cardiac allograft model. This discrepancy might be explained by the immunogenecity of the adenoviral vector, and the ability of liposome mediated IL-10 delivery to reduce lung AR is currently under investigation.