Lipid-Mediated Transbronchial Human Interleukin-10 Gene Transfer Decreases Acute Inflammation Associated With Allograft Rejection in a Rat Model of Lung Transplantation

Background: Transferring genes with immunoregulatory capacity to transplanted organs has the potential to modify allograft rejection (AR). We examined the effect of ex vivo lipid-mediated transbronchial human interleukin-10 (hIL-10) gene transfer on acute AR in a rat model of lung transplantation. Methods: Left single lung transplantations were performed between a highly histoincompatible rat combination: Brown Norway to Lewis. The extracted donor left lung was intrabronchially instilled with a plasmid encoding hIL-10 or Escherichia coli β-galactosidase (control), mixed with a cationic lipid. On day 6 posttransplantation, the degree of AR was graded histologically (stages 1-4) based upon pathological categories of inflammation: perivascular, peribronchial, and peribronchiolar lymphocytic infiltrates, edema, intraalveolar hemorrhage, and necrosis. Results: The stage of AR in the IL-10 group (3.1 ± 0.4) was significantly lower than the control group (3.8 ± 0.4). Pathological scores for edema, intraalveolar hemorrhage, and necrosis in the IL-10 group (2.3 ± 0.8, 0.3 ± 0.5, and 0.3 ± 0.5, respectively) were also significantly decreased compared with those in the control group (3.2 ± 0.4, 2.2 ± 0.8, and 1.2 ± 0.4, respectively). Conclusion: Ex vivo lipid-mediated transbronchial hIL-10 gene transfer attenuated acute inflammation associated with AR in a rat model of lung transplantation.