Liposomal IGF-1 gene transfer modulates pro- and anti-inflammatory cytokine mRNA expression in the burn wound

M. Spies, O. Nesic, R. E. Barrow, J. R. Perez-Polo, D. N. Herndon

Research output: Contribution to journalArticle

56 Scopus citations

Abstract

The use of systemic IGF-1 has been shown to attenuate the postburn hypermetabolic response and improve burn wound healing. Local IGF-1 gene therapy, however, promotes re-epithelialization in the burn wound without the side-effects associated with systemic delivery. We tested the hypothesis that these beneficial effects are due to changes in local cytokine production. Adult male Sprague-Dawley rats received a 40% total body surface area full-thickness scald burn and randomly received a subcutaneous injection at the burn wound margin of saline or cationic liposomes containing a IGF-1 cDNA construct. Animals were killed at 1, 4, 7 and 10 days after burn trauma. Skin biopsies at the wound border were harvested for total RNA extraction. Cytokine mRNA expression was determined using a multi-probe RNase protection assay. Data are presented as means ± s.e.m. Statistical analysis used the unpaired t-test or Mann-Whitney test where appropriate. Significance was accepted at P < 0.05. Treatment of the burn wound with liposomal IGF-1-cDNA transfer decreased IL-1β mRNA levels on day 10 after burn trauma from five-fold burn-induced increases compared with sham-treated rats, to near the control values present in unburned skin samples. Similarly, there was an eight-fold increase in TNF-α mRNA expression on postburn day 10 that was abrogated by IGF-1 gene therapy. Local IGF-1 gene transfer attenuates the mRNA expression of the inflammatory cytokines IL-1β and TNF-α in the burn wound. This change may improve burn wound healing by decreasing prolonged local inflammation.

Original languageEnglish (US)
Pages (from-to)1409-1415
Number of pages7
JournalGene Therapy
Volume8
Issue number18
DOIs
StatePublished - Oct 6 2001

Keywords

  • Burn wound
  • Cytokines
  • Gene therapy
  • IGF-1
  • Liposomes

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

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