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.

Abstract

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.

• Authors: Hisashi Oishi, Yoshinori Okada, Toshiaki Kikuchi, Yasushi Hoshikawa, Tetsu Sado, Masafumi Noda, Chiaki Endo, Akira Sakurada, Yuji Matsumura, Takashi Kondo
• Journal: The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation (J Heart Lung Transplant) Vol. 29 Issue 3 Pg. 360-7 (Mar 2010) ISSN: 1557-3117 [Electronic] United States
• PMID: 20202600 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Interleukin-2
• Lipids
• Tumor Necrosis Factor-alpha
• Interleukin-10

Topics

• Animals
• Gene Expression
• Gene Transfer Techniques
• Genetic Therapy
• Graft Rejection (metabolism, pathology)
• Humans
• Inflammation (metabolism, pathology, prevention & control)
• Interleukin-10 (genetics, metabolism)
• Interleukin-2 (genetics, metabolism)
• Lipids
• Lung (metabolism, pathology)
• Lung Transplantation (pathology)
• Male
• Models, Animal
• Plasmids
• Rats
• Rats, Inbred BN
• Rats, Inbred Lew
• Transplantation, Homologous
• Tumor Necrosis Factor-alpha (genetics, metabolism)