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

• Published in: Gene therapy Vol. 8; no. 18; pp. 1409 - 1415
• Main Authors: SPIES, M, NESIC, O, BARROW, R. E, PEREZ-POLO, J. R, HERNDON, D. N
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing Group 01.09.2001
• Subjects: Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Animals; Applied cell therapy and gene therapy; Biological and medical sciences; Biopsy; Biotechnology; Burns - therapy; Cytokines; Cytokines - genetics; Fundamental and applied biological sciences. Psychology; Gene Expression; Gene therapy; Genetic Therapy - methods; Health. Pharmaceutical industry; IL-1β; Industrial applications and implications. Economical aspects; Inflammation; Injections, Subcutaneous; Insulin-like growth factor I; Insulin-Like Growth Factor I - genetics; Interleukin-1 - genetics; Liposomes; Male; Medical sciences; Random Allocation; Rats; Rats, Sprague-Dawley; RNA, Messenger - metabolism; Scald; Statistical analysis; Statistics, Nonparametric; Transfusions. Complications. Transfusion reactions. Cell and gene therapy; Trauma; Tumor Necrosis Factor-alpha - genetics; Tumor necrosis factor-α; Wound healing; Rat; Rodentia; Cytokine; Liposome; Gene expression; Insulin like growth factor 1; Genetic transfer; Burn; Vertebrata; Mammalia; Subcutaneous administration; Gene therapy; Vector
• ISSN: 0969-7128; 1476-5462
• DOI: 10.1038/sj.gt.3301543

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-1beta 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-alpha 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-1beta and TNF-alpha in the burn wound. This change may improve burn wound healing by decreasing prolonged local inflammation.