Recipient intramuscular cotransfection of naked plasmid transforming growth factor ß1 and interleukin 10 ameliorates lung graft ischemia-reperfusion injury

Objective: Multiple gene transfer might permit modulation of concurrent biochemical pathways involved in acute lung graft rejection. We investigated whether gene cotransfection into the recipient reduces acute lung graft rejection. Methods: Brown Norway rats were used as donors, and F344 rats were used as recipients. Recipient animals were injected with saline (groups I/VI) or 1 1010 pfu of adenovirus encoding -galactosidase (groups II/VII), transforming growth factor 1 (groups III/VIII), interleukin 10 (groups IV/IX), or both transforming growth factor 1 and interleukin 10 (groups V/X) into both leg muscles 2 days before transplantation (groups I-V) or at the time of harvest (groups VI-X). The Kruskal- Wallis test for rejection score and 1-way analysis of variance were used to compare groups. Results: Oxygenation was significantly improved in the cotransfected groups treated 2 days before transplantation and at the time of harvest. Rejection scores were also reduced in the cotransfected groups. In group V cotransfection suppressed endogenous interleukin 2 but not interferon and tumor necrosis factor. Conclusion: Recipient intramuscular cotransfection of transforming growth factor 1 and interleukin 10 suppressed interleukin 2 expression and provided a synergistic effect that reduced acute lung graft rejection. This approach might be applied to the clinical setting because transplant recipients could be treated at the time of implantation.