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Anti-inflammatory gene therapy in the donor improves graft function after lung transplantation
  1. A Fisher
  1. Consultant Respiratory and Transplant Physician, Freeman Hospital, Newcastle upon Tyne, UK; A.J.Fishernewcastle.ac.uk

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Ischaemia-reperfusion injury remains an important cause of primary graft failure and early mortality after lung transplantation. Interleukin (IL)-1, an early response and potent pro-inflammatory cytokine, has been implicated in the pathophysiology. In this paper the role of transfection of donor lungs with an adenoviral vector for soluble type I IL-1 receptor, a competitive inhibitor of IL-1 activity, was investigated. Donor rodents were treated endobronchially with vector encoding soluble type I IL-1 receptor (n = 6), vector alone (n = 6), or normal saline (n = 6). Donor lungs were harvested after 24 hours and stored for a further 18 hours to exaggerate the cold ischaemic insult. The lungs were then implanted into recipient animals and, 24 hours after reperfusion, oxygenation (Pao2), lung oedema (wet-dry ratio) and neutrophil infiltration (myeloperoxidase activity) were assessed to determine the extent of acute lung injury. Graft oxygenation was significantly increased and myeloperoxidase activity significantly reduced in the transfected group compared with either the vector or saline controls. Lung oedema was also reduced but did not achieve statistical significance. Significant expression of soluble IL-1 receptor was demonstrated by immunochemistry in the transfected donor lungs but not in controls.

This study shows that anti-inflammatory gene therapy can be delivered to the airway in an animal model and can subsequently successfully disrupt the pro-inflammatory cascade in the lung. The implications of this work extend beyond the protection of early graft function after lung transplantation to include other clinical scenarios associated with acute lung injury.

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