Novel action of indoleamine 2,3-dioxygenase attenuating acute lung allograft injury

Am J Respir Crit Care Med. 2006 Mar 1;173(5):566-72. doi: 10.1164/rccm.200509-1413OC. Epub 2005 Nov 17.


Rationale: Lung allografts are prone to reperfusion injury and acute rejection, which, in addition to infiltrating lymphocytes, are accompanied by neutrophil infiltration and neutrophil-associated oxidative stress. Indoleamine 2,3-dioxygenase (IDO) is a unique cytosolic enzyme that possesses T-cell-suppressive and antioxidant properties.

Objectives: The purpose of this study was to determine if genetic up-regulation of IDO could ameliorate acute lung allograft injury.

Methods: Lung orthotopic transplants were performed using Lewis donors and Sprague-Dawley rat recipients (allografts) or the same strain (isografts). Plasmid-encoding human IDO was delivered to donor lungs in vivo using a nonviral gene-transfer vector, polyethylenimine. Transplanted lungs were evaluated at 6 d post-transplantation based on pulmonary function, histology, inflammatory responses, and their associated oxidative stress. Basic biology of the IDO-overexpressing lung cells was evaluated in vitro in response to external oxidant.

Measurements and main results: This gene delivery method led to uniform transgene expression in lung tissue distributed in airway, alveolar epithelial, and endothelial cells. IDO overexpression in lung allografts resulted in a significant protective effect with improvement in functional properties (peak airway pressure and oxygenation) and histologic appearance. Although IDO was able to block local T-cell responses, it failed to abrogate neutrophilic infiltration and the inflammation-associated oxidative stress. IDO-enhanced lung cells were resistance to oxidant-induced necrosis and apoptosis by limiting intracellular reactive oxygen species formation.

Conclusions: These results demonstrate that IDO prevents acute lung allograft injury through augmenting the local antioxidant defense system and inhibiting alloreactive T-cell responses.

MeSH terms

  • Acute Disease
  • Animals
  • Genetic Therapy*
  • Indoleamine-Pyrrole 2,3,-Dioxygenase / genetics*
  • Lung Transplantation / adverse effects*
  • Male
  • Postoperative Complications / immunology
  • Postoperative Complications / prevention & control*
  • Rats
  • Rats, Inbred Lew
  • Rats, Sprague-Dawley


  • Indoleamine-Pyrrole 2,3,-Dioxygenase