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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

In vivo transtracheal adenovirus-mediated transfer of human interleukin-10 gene 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) 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 x 10(9) PFU of Ad5E1RSVhIL-10, groups 2 and 5 received 5 x 10(9) 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 degrees 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 alpha (rTNF-alpha), interferon gamma ( IFN-gamma), 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-alpha and INF-gamma 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.[1]

References

  1. In vivo transtracheal adenovirus-mediated transfer of human interleukin-10 gene to donor lungs ameliorates ischemia-reperfusion injury and improves early posttransplant graft function in the rat. Fischer, S., Liu, M., MacLean, A.A., de Perrot, M., Ho, M., Cardella, J.A., Zhang, X.M., Bai, X.H., Suga, M., Imai, Y., Keshavjee, S. Hum. Gene Ther. (2001) [Pubmed]
 
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