2004 Fiscal Year Final Research Report Summary
Interleukin-10 Gene Transfer to The Airway of Rat Lungs for Prevention of Lung Allograft Rejection
| Project/Area Number |
14370401
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Thoracic surgery
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| Research Institution | Tohoku University |
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Principal Investigator |
OKADA Yoshinori Tohoku University, Institute of Development, Aging and Cancer, Thoracic Surgery, Research Associate, 加齢医学研究所, 助手 (90323104)
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| Co-Investigator(Kenkyū-buntansha) |
KONDO Takashi Tohoku University, Institute of Development, Aging and Cancer, Thoracic Surgery, Professor, 加齢医学研究所, 教授 (10195901)
MATSUMURA Yuji Tohoku University, Institute of Development, Aging and Cancer, Thoracic Surgery, Associate Professor, 加齢医学研究所, 助教授 (80281997)
HOSHIKAWA Yasushi Tohoku University, Hospital, Thoracic Surgery, Research Associate, 病院・助手 (90333814)
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| Project Period (FY) |
2002 – 2004
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| Keywords | lung transplanation / allograft rejection / tolerance / gene transfer / IL-10 |
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| Research Abstract |
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.
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Research Products
(9 results)
