Transbronchial human interleukin-10 gene transfer reduces acute inflammation associated with allograft rejection and intragraft interleukin-2 and tumor necrosis factor-α gene expression in a rat model of lung transplantation

• Published in: The Journal of heart and lung transplantation Vol. 29; no. 3; pp. 360 - 367
• Main Authors: Oishi, Hisashi, MD, PhD, Okada, Yoshinori, MD, PhD, Kikuchi, Toshiaki, MD, PhD, Hoshikawa, Yasushi, MD, PhD, Sado, Tetsu, MD, PhD, Noda, Masafumi, MD, PhD, Endo, Chiaki, MD, PhD, Sakurada, Akira, MD, PhD, Matsumura, Yuji, MD, PhD, Kondo, Takashi, MD, PhD
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.03.2010
• Subjects: allograft rejection; Animals; Gene Expression; Gene Transfer Techniques; Genetic Therapy; Graft Rejection - metabolism; Graft Rejection - pathology; Humans; Inflammation - metabolism; Inflammation - pathology; Inflammation - prevention & control; interleukin-10; Interleukin-10 - genetics; Interleukin-10 - metabolism; interleukin-2; Interleukin-2 - genetics; Interleukin-2 - metabolism; Lipids; Lung - metabolism; Lung - pathology; lung transplantation; Lung Transplantation - pathology; Male; Models, Animal; Plasmids; Rats; Rats, Inbred BN; Rats, Inbred Lew; Surgery; transbronchial gene transfer; Transplantation, Homologous; Tumor Necrosis Factor-alpha - genetics; Tumor Necrosis Factor-alpha - metabolism; tumor necrosis factor-α (alfa); interleukin-2; lung transplantation; tumor necrosis factor-α (alfa); interleukin-10; allograft rejection; transbronchial gene transfer
• ISSN: 1053-2498; 1557-3117
• DOI: 10.1016/j.healun.2009.10.002

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 β-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-α 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.