Diminished Interleukin-8 (IL-8) Production in the Fetal Wound Healing Response

Abstract

Background.Fetal skin wound healing results in scarless repair with minimal cellular inflammatory response. Interleukin-8 (IL-8) stimulates inflammation in postnatal wound healing but little is known about its role in fetal wounds. We hypothesized that fetal tissues have diminished IL-8 during wound repair and in response to platelet-derived growth factor (PDGF), a growth factor central to wound healing.Materials and methods.To examine the IL-8 response of fibroblasts to PDGF, cultures of human fetal (17–18 weeks) and adult dermal fibroblasts were incubated 8 h with PDGF (0, 0.1, 1, or 10 ng/mL) and supernatants and cells were collected for IL-8 ELISA and IL-8 RT-PCR. To evaluate the IL-8 response to wounding, human adult and fetal skin was placed subcutaneously in the SCID mouse, wounded, and the wound cleft excised after 4, 12, 24, or 72 h for IL-8 RT-PCR.Results.Fetal fibroblasts produced less IL-8 protein at baseline (50 ± 6 pg/mL versus 450 ± 115 pg/mL,P< 0.001) and in response to all concentrations of PDGF examined (P< 0.001). IL-8 mRNA was detected in unstimulated adult fibroblasts but not in fetal fibroblasts. Much less IL-8 mRNA was detected in stimulated fetal fibroblasts than in adult fibroblasts. IL-8 mRNA was detected 4 h after wounding in fetal and adult wounds. By 12 h no IL-8 mRNA was detected in fetal wounds, whereas adult wounds had IL-8 mRNA persisting to 72 h.Conclusions.Diminished inflammatory cytokine response by fetal tissues may be responsible for the lack of cellular recruitment and inflammation seen in fetal wound healing and may contribute to scarless wound repair.