In VivoTranstracheal Adenovirus-Mediated Transfer of Human Interleukin-10 Gene to Donor Lungs Ameliorates Ischemia-Reperfusion Injury and Improves Early Posttransplant Graft Function in the Rat

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Abstract
We examined the effect of adenovirus-mediated transtracheal transfer of the human interleukin 10 (hIL-10) gene on lung ischemia-reperfusion (IR) injury, which is the insult due to hypothermic preservation plus graft reperfusion, and posttransplant lung function in Lewis rat lungs. Thirty rats were divided into 6 groups (n = 5). Groups 1 and 4 received 5 × 109 PFU of Ad5E1RSVhIL-10, groups 2 and 5 received 5 × 109 PFU of Ad5BGL2 ("empty" vector), and groups 3 and 6 received 3% sucrose (diluent). After 24 hr of in vivo transfection, lungs were stored at 4°C (cold ischemic time, CIT) for 6 hr (groups 1-3) or 24 hr (groups 4-6) before transplantation. After 2 hr of reperfusion, lung function was assessed by oxygenation (FIo2, 1.0), airway pressure (AwP), and wet-to-dry (W/D) weight ratios. Rat tumor necrosis factor α (rTNF-α), interferon γ (IFN-γ), IL-10, and hIL-10 were measured in graft tissue and recipient plasma by ELISA and detected by immunohistochemistry (IHC). Partial pressure of oxygen (Pao2) levels in the hIL-10 group (6 hr of CIT) were higher than in empty vector and diluent groups (Pao2, 530 ± 23 vs. 387 ± 31 and 439 ± 27 mmHg, respectively, p < 0.05). IL-10 rats after 24 hr of CIT showed higher Pao2 levels (260 ± 29 mmHg) than empty vector (96 ± 24 mmHg) or diluent (133 ± 10 mmHg) lungs (p < 0.05). AwP and W/D ratios were reduced in hIL10 lungs (p < 0.05) compared with the other groups. rTNF-α and INF-γ were reduced in tissue and plasma in groups 1 and 4 (p < 0.05). rIL-10 was reduced in the tissue of hIL-10 lungs (p < 0.05). IHC showed equal distribution of cytokines in tissue and abundant transgene expression in large and small airway epithelium in hIL-10 lungs.