HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Sekhar Dharmarajan Hideki Itano G. Alexander Patterson Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Tagawa, T. Articles by Patterson, G. A. Search for Related Content PubMed PubMed Citation Articles by Tagawa, T. Articles by Patterson, G. A.

Ann Thorac Surg 2004;78:1932-1939
© 2004 The Society of Thoracic Surgeons

---

Original Article: General Thoracic

Endobronchial Gene Transfer of Soluble Type I Interleukin-1 Receptor Ameliorates Lung Graft Ischemia-Reperfusion Injury

^a Division of Cardiothoracic Surgery, Department of Surgery, Washington University School of Medicine, St. Louis, Missouri, USA
^b First Department of Surgery, Nagasaki University School of Medicine, Nagasaki, Japan

Accepted for publication June 7, 2004.

^* Address reprint requests to Dr Patterson, Division of Cardiothoracic Surgery, Washington University School of Medicine, One Barnes-Jewish Hospital Plaza, 3108 Queeny Tower, St. Louis, MO 63110-1013 (E-mail: pattersona{at}msnotes.wustl.edu).

Presented at the Fortieth Annual Meeting of The Society of Thoracic Surgeons, San Antonio, TX, Jan 26–28, 2004.

BACKGROUND: Soluble type I interleukin-1 receptor is a competitive inhibitor of interleukin-1 and may reduce its proinflammatory actions. The objective of this experiment was to demonstrate that endobronchial gene transfer of soluble type I interleukin-1 receptor IgG to donor lung grafts reduces posttransplant ischemia-reperfusion injury.

METHODS: All experiments utilized an orthotopic left lung isograft transplant model. Donors were divided into three groups (n = 6 each) for endobronchial transfection: group I received 2 x 10⁷ plaque-forming units of adenovirus encoding soluble type I interleukin-1 receptor IgG; group II received 2 x 10⁷ plaque-forming units of nonfunctional control adenovirus encoding ß-galactosidase; and group III received 0.1 mL of saline. Left lungs were harvested 24 hours after transfection and stored for 18 hours before transplantation. Graft function was assessed 24 hours after reperfusion using three measurements: isolated graft oxygenation, wet-to-dry lung weight ratio, and tissue myeloperoxidase activity. Transgene expression of soluble type I interleukin-1 receptor IgG was also evaluated using enzyme-linked immunosorbent assay and immunohistochemistry.

RESULTS: Isolated graft arterial oxygenation was significantly improved in group I compared with groups II and III (281.8 ± 134.8 versus 115.7 ± 121.5 and 88.0 ± 58.9 mm Hg, p = 0.0197 and p = 0.0081, respectively). Myeloperoxidase activity was also significantly reduced in group I compared with groups II and III (0.083 ± 0.044 versus 0.155 ± 0.043 and 0.212 ± 0.079 optical density units per minute per milligram protein, p = 0.0485 and p = 0.0016, respectively). Expression of soluble type I interleukin-1 receptor IgG was detected only in lungs from group I.

CONCLUSIONS: Endobronchial gene transfer of soluble type I interleukin-1 receptor IgG to donor lung grafts subjected to prolonged cold ischemia ameliorates ischemia-reperfusion injury by improving graft oxygenation and reducing lung edema and neutrophil sequestration.

This article has been cited by other articles:

				A Fisher Anti-inflammatory gene therapy in the donor improves graft function after lung transplantation Thorax, April 1, 2005; 60(4): 319 - 319. [Full Text] [PDF]