Muscle-targeted transfer of plasmid DNA for suppression of chronic rejection after lung transplantation

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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.