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

Abstract

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. 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. 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. 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.