Attenuation of lung injury in allograft rejection using NF-κB decoy transfection -: novel strategy for use in lung transplantation

Objective: Increased production of nitric oxide (NO) is known to be a marker of lung allograft rejection and lung injury. NO production is up-regulated directly or indirectly by nuclear factor-kappa B (NF-kappaB), a transcriptional factor of inflammatory cytokines and iNOS. We attempted to determine whether transfection of an NF-kappaB decoy into allografts could reduce NO production and ameliorate acute lung injury during altograft rejection. Methods: Left lung transplantation was performed in pairs of Brown Norway (RT1(n)) and Lewis (RT1) rats. In Group NF (n = 6), the attografts were flushed with 20 ml of PBS solution containing a hemagglutinating virus of Japan (HVJ) tiposome-ODN complex as an NF-kappaB decoy and preserved for 60 min at 4 degreesC. A scramble decoy was used in the positive control (Group S, n = 5) and simple PBS solution in the negative control (Group C, n = 5). Five days after transplantation without use of immuno-suppressants, exhaled NO, gas exchange, and graft histological rejection score were determined. Results: The exhaled NO level was significantly reduced in Group NF as compared with Group S (445 +/- 162 vs 1305 +/- 123 ppb, P < 0.02), while improvements in PaO2 (197 +/- 28 vs. 60 +/- 18 mmHg, P < 0.02) and rejection score (1.8 +/- 0.3 vs. 2.5 +/- 0.4) were also observed. There were no differences in these parameters between Groups S and C. Conclusions: Inhibition of NF-kappaB activation in the altograft by ODN decoy transfection into the donor lung ameliorated lung injury during acute allograft rejection. Our results imply a possible therapeutic target for the inflammation process in lung transplantation clinical settings. (C) 2004 Elsevier B.V. All rights reserved.