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

Gene Therapy volume 8, pages 1409–1415 (2001)Cite this article

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. Gene Therapy (2001) 8, 1409–1415.

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Acknowledgements

The study was supported by the Clayton Foundation of Research, Houston, TX, and the Shriners Hospitals for Children.

Part of the data was presented at the 33rd Annual Meeting of the American Burn Association in Boston on 18–21 April 2001.

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Authors and Affiliations

  1. Department of Surgery, Shriners Hospitals for Children, Galveston, TX, USA

    M Spies, RE Barrow & DN Herndon

  2. Department of Human Biological Chemistry and Genetics, The University of Texas Medical Branch, Galveston, TX, USA

    O Nesic & JR Perez-Polo

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Spies, M., Nesic, O., Barrow, R. et al. Liposomal IGF-1 gene transfer modulates pro- and anti-inflammatory cytokine mRNA expression in the burn wound. Gene Ther 8, 1409–1415 (2001). https://doi.org/10.1038/sj.gt.3301543

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