2001 Fiscal Year Final Research Report Summary
Muscle-targeted transfer of plasmid DNA for suppression of chronic rejection after lung transplantation
| Project/Area Number |
12671300
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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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 | Niigata University |
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Principal Investigator |
TSUCHIDA Masanori Medical Hospital, Niigata University, Lecturer, 医学部・附属病院, 講師 (60293221)
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| Co-Investigator(Kenkyū-buntansha) |
AOKI Tadashi Medical Hospital, Niigata University, Assistant, 医学部・附属病院, 助手 (20334659)
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| Project Period (FY) |
2000 – 2001
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| Keywords | Gene transfer / Electroporation / IL-10 / Tracheal transplantation |
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| Research Abstract |
Long-term survival after lung transplantation is limited mainly by bronchiolitis obliterans, which is regarded as a form of chronic rejection. To examine whether anti-inflammatory cytokine prevents chronic rejection, we transferred mouse and viral IL-10 to the recipient animals that were transplanted with tracheal allografts. Naked plasmid DNA containing mouse or viral IL-10 was transferred to the animal by intramuscular injection followed by electroporation. After intramuscular injection, the serum levels of IL-10 and the duration of cytokine expression were examined. After 72 hours, IL-10 level reached peak and could be detected until 2 weeks. We next examined preventive effects of IL-10 on chronic rejection. Histology and degree of luminal obliteration of the trachea were studied in the animals with or without expression ofIL-10. Although there are several animals that have improved luminal obliteration, the preventive effects varied among animals. To maintain the level of IL-10 high for 4 weeks, genes were transferred 4 times after tracheal transplantation. However, consistent improvement was not obtained. Although there may be possibility of prevention of bronciotitis obliterans by inducing IL-10 in vivo, it's effect was not consistent and combination therapy with other cytokines should be considered.
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