Intramuscular gene transfer of interleukin-10 reduces neutrophil recruitment and ameliorates lung graft ischemia-reperfusion injury

Benjamin D. Kozower, Samer A. Kanaan, Tsutomu Tagawa, Takashi Suda, Kathleen Grapperhaus, Niccolo Daddi, Erika C. Crouch, Claire M. Doerschuk, G. Alexander Patterson

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

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 × 1010 plaque-forming units (pfu) adenovirus encoding human IL-10 (hIL-10), 1 × 1010 pfu adenovirus control encoding p-galactosidase, or saline. Gene expression in muscle and plasma was confirmed. Lung grafts were harvested, stored at 4°C for 18h, and assessed 24h after transplantation. Peak muscle and plasma expression of hIL-10 was achieved 24h 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.

Original languageEnglish
Pages (from-to)837-842
Number of pages6
JournalAmerican Journal of Transplantation
Volume2
Issue number9
DOIs
Publication statusPublished - 10-2002

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Transplantation
  • Pharmacology (medical)

Fingerprint Dive into the research topics of 'Intramuscular gene transfer of interleukin-10 reduces neutrophil recruitment and ameliorates lung graft ischemia-reperfusion injury'. Together they form a unique fingerprint.

  • Cite this

    Kozower, B. D., Kanaan, S. A., Tagawa, T., Suda, T., Grapperhaus, K., Daddi, N., Crouch, E. C., Doerschuk, C. M., & Patterson, G. A. (2002). Intramuscular gene transfer of interleukin-10 reduces neutrophil recruitment and ameliorates lung graft ischemia-reperfusion injury. American Journal of Transplantation, 2(9), 837-842. https://doi.org/10.1034/j.1600-6143.2002.20905.x