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 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.
Spies
M
M
Department of Surgery, Shriners Hospitals for Children, Galveston, TX 77550, USA.
Nesic
O
O
Barrow
R E
RE
Perez-Polo
J R
JR
Herndon
D N
DN
D000818:Animals; D002056:Burns / Q000628:therapy*; D016207:Cytokines / Q000235:genetics*; D015870:Gene Expression; D015316:Genetic Therapy / Q000379:methods*; D007279:Injections, Subcutaneous; D007334:Insulin-Like Growth Factor I / Q000235:genetics*; D007375:Interleukin-1 / Q000235:genetics; D008081:Liposomes; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D018709:Statistics, Nonparametric; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D016207:Cytokines; D007375:Interleukin-1; D008081:Liposomes; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D007334:Insulin-Like Growth Factor I