In vivo transtracheal adenovirus-mediated transfer of human interleukin-10gene to donor lungs ameliorates ischemia-reperfusion injury and improves early posttransplant graft function in the rat

We examined the effect of adenovirus-mediated transtracheal transfer of the human interleukin 10 (hIL-10) gene on lung ischemia-reperfusion (IR) injur y, which is the insult due to hypothermic preservation plus graft reperfusi on, and posttransplant lung function in Lewis rat lungs. Thirty rats were d ivided into 6 groups (n = 5). Groups 1 and 4 received 5 X 10(9) PFU of Ad5E 1RSVhIL-10, groups 2 and 5 received 5 X 10(9) PFU of Ad5BGL2 ("empty" vecto r), and groups 3 and 6 received 3% sucrose (diluent). After 24 hr of in viv o transfection, lungs were stored at 4 degreesC (cold ischemic time, CIT) f or 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), a irway pressure (AwP), and wet-to-dry (W/D) weight ratios. Rat tumor necrosi s factor alpha (rTNF-alpha), interferon gamma (IFN-gamma), IL-10, and hIL-1 0 were measured in graft tissue and recipient plasma by ELISA and detected by immunohistochemistry (IHC). Partial pressure of oxygen (Pa-o2) levels in the hIL-10 group (6 hr of CIT) were higher than in empty vector and diluen t groups (Pa-o2, 530 +/- 23 vs. 387 +/- 31 and 439 +/- 27 mmHg, respectivel y, p < 0.05). IL-10 rats after 24 hr of CIT showed higher Pa-o2 levels (260 +/- 29 mmHg) than empty vector (96 +/- 24 mmHg) or diluent (133 +/- 10 mmH g) lungs (p < 0.05). AwP and W/D ratios were reduced in hIL-10 lungs (p < 0 .05) compared with the other groups. rTNF-<alpha> and INF-gamma were reduce d 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 cyt okines in tissue and abundant transgene expression in large and small airwa y epithelium in hIL-10 lungs.