Interleukin-10 Gene Transfer to The Airway of Rat Lungs for Prevention of Lung Allograft Rejection

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Background : The ability to express genes with potential immunoregulatory capacity could reduce allograft rejection (AR). We examined the feasibility of transferring the vIL-10 gene into rat lungs by intra-bronchial instillation and the subsequent effects of delivered vIL-10 on acute lung AR. Methods : First, the adenoviral β-galactosidase vector (adv-β-gal) particles were instilled into the rat lung and protein synthesis of β-gal was confirmed by histochemical staining. Next, the ability of the adenoviral vIL-10 vector (adv-vIL-10) transfection to modify AR was examined in a highly histoincompatible rat lung transplant model (BN→Lew). Donor left lungs were transfected with 3x10^8 pfu/0.3mL of adv-vIL-10 or adv-β-gal 3 days before transplantation. On day 6 post-transplant, AR was graded histologically (stage 0-4). Several pathological categories of inflammation were also scored on a scale of 0-4. Results : The stage of AR was 3.75±0.5 in the adv-vIL-10 group and 4.0±0 in the adv-β-gal group, and the difference did not reach a statistically significant difference. There were no significant differences either in the degree of edema (3.5±0.6 vs. 4±0), vasculitis (1.5±0.6 vs. 1.5±0.6), necrosis (1.5±0.5 vs. 1.75±1.3), and hemorrhage (2.3±1.0 vs. 2.5±0.6). Conclusion : This preliminary study showed that transfection of adv-vIL-10 did not seem to reduce lung AR significantly, as opposed to the results of our previous experiments in a rat cardiac allograft model. This discrepancy might be explained by the immunogenecity of the adenoviral vector, and the ability of liposome mediated IL-10 delivery to reduce lung AR is currently under investigation.