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 beta-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).


CONCLUSIONS
Ex vivo lipid-mediated transbronchial hIL-10 gene transfer attenuated acute inflammation associated with AR in a rat model of lung transplantation.
Oishi
H
H
Department of Thoracic Surgery, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Miyagi, Japan. bigstone@idac.tohoku.ac.jp
Okada
Y
Y
Kikuchi
T
T
Sado
T
T
Oyaizu
T
T
Hoshikawa
Y
Y
Suzuki
S
S
Matsumura
Y
Y
Kondo
T
T
D000818:Animals; D018014:Gene Transfer Techniques; D006084:Graft Rejection / Q000276:immunology* / Q000517:prevention & control*; D007249:Inflammation / Q000517:prevention & control*; D016753:Interleukin-10 / Q000235:genetics*; D016040:Lung Transplantation / Q000276:immunology* / Q000473:pathology; D008297:Male; D023421:Models, Animal; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D012086:Reoperation; D014184:Transplantation, Homologous / Q000276:immunology*
D016753:Interleukin-10