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

The use of systemic IGF-1 has been shown to attenuate the postburn hypermet abolic response and improve burn wound healing. Local IGF-1 gene therapy, h owever, promotes reepithelialization in the burn wound without the side-eff ects 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-thickn ess scald burn and randomly received a subcutaneous injection at the burn w ound margin of saline or cationic liposomes containing a IGF-1 cDNA constru ct. Animals were killed at 1, 4, 7 and 10 days after burn trauma. Skin biop sies 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 unpaire d 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-1<beta> mRNA levels on day 10 after burn trauma from five-fol d bum-induced increases compared with sham-treated rats, to near the contro l values present in unburned skin samples. Similarly, there was an eight-fo ld increase in TNF-alpha mRNA expression on postburn day 10 that was abroga ted by IGF-1 gene therapy. Local IGF-1 gene transfer attenuates the mRNA ex pression of the inflammatory cytokines IL-1 beta and TNF-alpha in the burn wound. This change may improve burn wound healing by decreasing prolonged l ocal inflammation.