Transbronchial human interleukin-10 gene transfer reduces acute inflammation associated with allograft rejection and intragraft interleukin-2 and tumor necrosis factor-alpha gene expression in a rat model of lung transplantation.
BACKGROUND
The ability to express genes with potential immunoregulatory capacity could reduce allograft rejection (AR). This study examined the effect of ex vivo lipid-mediated transbronchial human interleukin-10 (hIL-10) gene transfer on AR and the intragraft cytokine profile in a rat model of lung transplantation.


METHODS
Left single lung transplants were performed between a highly histoincompatible combination of inbred rats. The donor left lung was extracted and intrabronchially instilled with a plasmid encoding hIL-10 (IL-10 group) or Escherichia coli beta-galactosidase (control group), mixed with a cationic lipid. At 3 and 6 days after transplantation, the degree of AR was graded histologically (stage 1-4) and several pathologic categories of inflammation were scored on a scale of 0 to 4 according to the percentage of involvement. Intragraft cytokine profile was examined by real-time reverse transcription polymerase chain reaction.


RESULTS
The stage of AR (3.1 +/- 0.4 vs 3.8 +/- 0.4) and the pathologic scores for edema (2.3 +/- 0.8 vs 3.2 +/- 0.4), intraalveolar hemorrhage (0.3 +/- 0.5 vs 2.2 +/- 0.8), and necrosis (0.3 +/- 0.5 vs 1.2 +/- 0.4) in the IL-10 group were significantly decreased compared with the control group at Day 6. IL-2 and tumor necrosis factor-alpha messenger RNA expression levels on Day 3 were significantly decreased in the IL-10 group.


CONCLUSIONS
Ex vivo lipid-mediated transbronchial hIL-10 gene transfer attenuated acute inflammation associated with AR, which was related to decreased levels of proinflammatory cytokine gene expression in a rat model of lung transplantation.
Oishi
Hisashi
H
Department of Thoracic Surgery, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan. bigstone@idac.tohoku.ac.jp
Okada
Yoshinori
Y
Kikuchi
Toshiaki
T
Hoshikawa
Yasushi
Y
Sado
Tetsu
T
Noda
Masafumi
M
Endo
Chiaki
C
Sakurada
Akira
A
Matsumura
Yuji
Y
Kondo
Takashi
T
D000818:Animals; D015870:Gene Expression; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D006084:Graft Rejection / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D016753:Interleukin-10 / Q000235:genetics* / Q000378:metabolism; D007376:Interleukin-2 / Q000235:genetics / Q000378:metabolism*; D008055:Lipids; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D016040:Lung Transplantation / Q000473:pathology; D008297:Male; D023421:Models, Animal; D010957:Plasmids; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D014184:Transplantation, Homologous; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*
D007376:Interleukin-2; D008055:Lipids; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10