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Right arrow Lung - transplantation

J Thorac Cardiovasc Surg 2005;129:926-931
© 2005 The American Association for Thoracic Surgery

Cardiothoracic Transplantation

Recipient intramuscular cotransfection of transforming growth factor ß1 and interleukin 10 ameliorates acute lung graft rejection

Takashi Suda, MDa, Niccoló Daddi, MDa, Tsutomu Tagawa, MDa, Samer A. Kanaan, MDa, Benjamin D. Kozower, MDa, Jon H. Ritter, MDb, G. Alexander Patterson, MD, FRCS(C)a,*

a Division of Cardiothoracic Surgery, Washington University School of Medicine, St Louis, Mo
b Department of Pathology, Washington University School of Medicine, St Louis, Mo

Received for publication March 18, 2004; revisions received July 8, 2004; accepted for publication July 13, 2004.

* Address for reprints: G. Alexander Patterson, MD, FRCS(C), Division of Cardiothoracic Surgery, Washington University School of Medicine, One Barnes-Jewish Hospital Plaza, 108 Queeny Tower, St Louis, MO 63110 (E-mail: pattersona{at}msnotes.wustl.edu).

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 1010 pfu of adenovirus encoding ß-galactosidase (groups II/VII), transforming growth factor ß1 (groups III/VIII), interleukin 10 (groups IV/IX), or both transforming growth factor ß1 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}.

CONCLUSION: Recipient intramuscular cotransfection of transforming growth factor ß1 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.






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