Muscle-targeted transfer of plasmid DNA for suppression of chronic rejection after lung transplantation

肺移植后的长期生存主要受到闭塞性细支气管炎的限制，这被认为是一种慢性排斥反应。为了研究抗炎细胞因子是否能预防慢性排斥反应，我们将小鼠和病毒IL-10转移到移植气管的受体动物身上。将含有小鼠或病毒IL-10的裸质粒DNA通过肌肉注射后电穿孔转移到动物体内。肌注后检测血清IL-10水平及细胞因子表达持续时间。72h后IL-10水平达到峰值，可检测至2周。我们接下来研究了IL-10对慢性排斥反应的预防作用。观察il -10表达和不表达小鼠的气管组织形态学和管腔闭塞程度。虽然有几种动物改善了腔隙闭塞，但动物之间的预防效果各不相同。为使IL-10维持高水平4周，气管移植后进行4次基因转移。然而，并没有得到持续的改善。虽然体内诱导IL-10有预防闭塞性支气管炎的可能，但其效果并不一致，应考虑与其他细胞因子联合治疗。

Long-term survival after lung transplantation is limited mainly by bronchiolitis obliterans, which is regarded as a form of chronic rejection. To examine whether anti-inflammatory cytokine prevents chronic rejection, we transferred mouse and viral IL-10 to the recipient animals that were transplanted with tracheal allografts. Naked plasmid DNA containing mouse or viral IL-10 was transferred to the animal by intramuscular injection followed by electroporation. After intramuscular injection, the serum levels of IL-10 and the duration of cytokine expression were examined. After 72 hours, IL-10 level reached peak and could be detected until 2 weeks. We next examined preventive effects of IL-10 on chronic rejection. Histology and degree of luminal obliteration of the trachea were studied in the animals with or without expression ofIL-10. Although there are several animals that have improved luminal obliteration, the preventive effects varied among animals. To maintain the level of IL-10 high for 4 weeks, genes were transferred 4 times after tracheal transplantation. However, consistent improvement was not obtained. Although there may be possibility of prevention of bronciotitis obliterans by inducing IL-10 in vivo, it's effect was not consistent and combination therapy with other cytokines should be considered.