Diminished interleukin-8 (IL-8) production in the fetal wound healing response.

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.

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.