Recipient intramuscular cotransfection of transforming growth factor beta1 and interleukin 10 ameliorates acute lung graft rejection.
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 x 10(10) pfu of adenovirus encoding beta-galactosidase (groups II/VII), transforming growth factor beta1 (groups III/VIII), interleukin 10 (groups IV/IX), or both transforming growth factor beta1 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 gamma and tumor necrosis factor alpha.


CONCLUSIONS
Recipient intramuscular cotransfection of transforming growth factor beta1 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.
Suda
Takashi
T
Division of Cardiothoracic Surgery, Washington University School of Medicine, St Louis, MO 63110, USA.
Daddi
Niccolo'
N
Tagawa
Tsutomu
T
Kanaan
Samer A
SA
Kozower
Benjamin D
BD
Ritter
Jon H
JH
Patterson
G Alexander
GA
D000208:Acute Disease; D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D005240:Feasibility Studies; D005822:Genetic Vectors; D006084:Graft Rejection / Q000473:pathology / Q000517:prevention & control*; D007273:Injections, Intramuscular; D007371:Interferon-gamma / Q000032:analysis; D016753:Interleukin-10 / Q000235:genetics*; D007376:Interleukin-2 / Q000032:analysis; D016040:Lung Transplantation / Q000473:pathology*; D010101:Oxygen Consumption / Q000502:physiology; D051381:Rats; D011914:Rats, Inbred BN; D011916:Rats, Inbred F344; D020858:Tissue and Organ Harvesting; D014162:Transfection / Q000379:methods*; D016212:Transforming Growth Factor beta / Q000235:genetics*; D053773:Transforming Growth Factor beta1; D014181:Transplantation Immunology / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D007376:Interleukin-2; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma