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Intramuscular Gene Transfer of Interleukin‐10 Reduces Neutrophil Recruitment and Ameliorates Lung Graft Ischemia‐Reperfusion Injury
Author(s) -
Kozower Benjamin D.,
Kanaan Samer A.,
Tagawa Tsutomu,
Suda Takashi,
Grapperhaus Kathleen,
Daddi Niccolo,
Crouch Erika C.,
Doerschuk Claire M.,
Patterson G. Alexander
Publication year - 2002
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1034/j.1600-6143.2002.20905.x
Subject(s) - medicine , gene transfer , immunology , ischemia , interleukin 1β , warm ischemia , interleukin , reperfusion injury , lung , pharmacology , gene , cytokine , biochemistry , chemistry
Interleukin‐10 (IL‐10) has potent anti‐inflammatory properties but its direct effects on neutrophil trafficking in lung transplant ischemia‐reperfusion (I/R) injury are unknown. This study was performed to determine if recipient intramuscular IL‐10 gene transfer reduces neutrophil infiltration in lung isografts and ameliorates I/R injury. Twenty‐four hours before transplantation, recipient rodents received intramuscular injection with 1 × 10 10 plaque‐forming units (pfu) adenovirus encoding human IL‐10 (hIL‐10), 1 × 10 10 pfu adenovirus control encoding β‐galactosidase, or saline. Gene expression in muscle and plasma was confirmed. Lung grafts were harvested, stored at 4 °C for 18 h, and assessed 24 h after transplantation. Peak muscle and plasma expression of hIL‐10 was achieved 24 h after gene transfer and returned to baseline by 7 days (p < 0.05 vs. controls). Gene transfer of hIL‐10 reduced neutrophil sequestration and emigration in lung grafts as measured by morphometry and myeloperoxidase activity (p < 0.03 vs. controls). Furthermore, hIL‐10 improved graft oxygenation and reduced lung edema (p < 0.01 vs. controls). Intramuscular gene transfer of hIL‐10 releases hIL‐10 protein into plasma and reduces neutrophil sequestration and emigration in lung isografts. This is associated with a reduction in I/R injury with improved isograft oxygenation and reduced tissue edema. Intramuscular gene transfer may be a useful strategy to reduce clinical I/R injury.