Transplant Immunosuppression Increases and Prolongs Transgene Expression in Adenoviral-Mediated Transfection of Rat Lungs

Cassivi, Stephen D.; Liu, M.; Boehler, Annette; Pierre, Andrew; Tanswell, A. Keith; O’Brodovich, Hugh; Slutsky, A. S.; Keshavjee, Shaf

doi:10.1097/00007890-199810270-00095

Transplantation

1998

DOI: 10.1097/00007890-199810270-00095

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Transplant Immunosuppression Increases and Prolongs Transgene Expression in Adenoviral-Mediated Transfection of Rat Lungs

Stephen D. Cassivi

M. Liu

Annette Boehler

et al.

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“…The release of proinflammatory cytokines secondary to the adenoviral vector use of gene therapy in the transplantation setting is faciliwas reduced by high-dose methylprednisolone (30 mg/kg) tated by the fact that the immunosuppressive therapy used administered 3 h before transfection. Reduction in the earlyto prevent graft rejection allows more effective and proadenoviral inflammatory response was associated with signifilonged transfection without developing immunization (8,9). …”

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Impact of Human Interleukin-10 on Vector-Induced Inflammation and Early Graft Function in Rat Lung Transplantation

Perrot

Fischer

Liu

et al. 2003

Am J Respir Cell Mol Biol

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This study was undertaken to examine the time course of human interleukin (hIL)-10 gene expression after transtracheal administration of adenoviral (Ad)hIL-10 and its effect on the early adenoviral proinflammatory cytokine response and on post-transplant lung function. Using a rat lung transplant model, we observed that lungs retrieved 12 h after the administration of AdhIL-10 were associated with significant improvement in post-transplant lung function. Shorter periods of transfection were associated with significantly elevated levels of tumor necrosis factor-alpha and macrophage inflammatory protein-2 in lung tissue, leading to an increased degree of injury. The release of proinflammatory cytokines secondary to the adenoviral vector was reduced by high-dose methylprednisolone (30 mg/kg) administered 3 h before transfection. Reduction in the early adenoviral inflammatory response was associated with significant improvement in post-transplant lung function when lungs were retrieved 6 or 12 h after transtracheal administration of AdhIL-10. Transtracheal administration of adenoviral-mediated hIL-10 to donor lungs is associated with a significant early inflammatory response that may enhance ischemia-reperfusion injury if insufficient hIL-10 is expressed in lung tissue before retrieval. The period between delivery of AdhIL-10 and lung retrieval can be reduced if the early inflammatory response is suppressed with methylprednisolone.

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mentioning

confidence: 99%

“…to prevent graft rejection allows more effective and proadenoviral inflammatory response was associated with signifilonged transfection without developing immunization (8,9).…”

mentioning

confidence: 99%

Impact of Human Interleukin-10 on Vector-Induced Inflammation and Early Graft Function in Rat Lung Transplantation

Perrot

Fischer

Liu

et al. 2003

Am J Respir Cell Mol Biol

View full text Add to dashboard Cite

show abstract

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Transplant Immunosuppression Increases and Prolongs Transgene Expression in Adenoviral-Mediated Transfection of Rat Lungs

Cited by 1 publication

References 0 publications

Impact of Human Interleukin-10 on Vector-Induced Inflammation and Early Graft Function in Rat Lung Transplantation

Impact of Human Interleukin-10 on Vector-Induced Inflammation and Early Graft Function in Rat Lung Transplantation

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