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, David Herndon

Research output: Contribution to journalArticle

54 Citations (Scopus)

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 - 2001

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Insulin-Like Growth Factor I
Anti-Inflammatory Agents
Cytokines
Messenger RNA
Wounds and Injuries
Genes
Interleukin-1
Genetic Therapy
Wound Healing
Complementary DNA
Re-Epithelialization
Skin
Body Surface Area
Subcutaneous Injections
Ribonucleases
Burns
Liposomes
Sprague Dawley Rats
RNA
Inflammation

Keywords

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

ASJC Scopus subject areas

  • Genetics

Cite this

Liposomal IGF-1 gene transfer modulates pro- and anti-inflammatory cytokine mRNA expression in the burn wound. / Spies, M.; Nesic, O.; Barrow, R. E.; Perez-Polo, J. R.; Herndon, David.

In: Gene Therapy, Vol. 8, No. 18, 2001, p. 1409-1415.

Research output: Contribution to journalArticle

Spies, M. ; Nesic, O. ; Barrow, R. E. ; Perez-Polo, J. R. ; Herndon, David. / Liposomal IGF-1 gene transfer modulates pro- and anti-inflammatory cytokine mRNA expression in the burn wound. In: Gene Therapy. 2001 ; Vol. 8, No. 18. pp. 1409-1415.
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