American Journal of Respiratory Cell and Molecular Biology. Vol. 28, pp. 616-625, 2003
© 2003 American Thoracic Society DOI: 10.1165/rcmb.2002-0109OC
Impact of Human Interleukin-10 on Vector-Induced Inflammation and Early Graft Function in Rat Lung Transplantation
Marc de Perrot,
Stefan Fischer,
Mingyao Liu,
Yumiko Imai,
Saulo Martins,
Shoji Sakiyama,
Toshi Tabata,
Xiao-Hui Bai,
Thomas K. Waddell,
Beverly L. Davidson and
Shaf Keshavjee
Thoracic Surgery Research Laboratory, Toronto General Hospital Research Institute, University Health Network, University of Toronto, Ontario, Canada; and The Gene Transfer Vector Core, Department of Medicine, University of Iowa, Iowa City, Iowa
Address correspondence to: S. Keshavjee, M.D., Director, Thoracic Surgery Research Laboratory, Toronto General Hospital, 200 Elizabeth Street, EN 10-224, Toronto, Ontario, Canada M5G 2C4. E-mail: shaf.keshavjee{at}uhn.on.ca
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- 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.
Abbreviations: cold ischemic time, CIT human IL-10, hIL-10 interferon, IFN interleukin, IL ischemia-reperfusion, IR low-potassium dextran, LPD main bronchus, MB macrophage inflammatory protein, MIP pulmonary artery, PA partial pressure of oxygen, PaO2 peak airway pressure, PawP positive end-expiratory pressure, PEEP pulmonary vein, PV Rous sarcoma virus, RSV tumor necrosis factor, TNF wet-to-dry, W/D
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