Diminished interleukin 6 (IL-6) production during scarless human fetal wound repair.
Fetal wound healing is characterized by minimal inflammation and scarless repair. IL-6 stimulates inflammation in postnatal wound healing. We hypothesized that fetal skin has a diminished IL-6 response and that exogenous IL-6 will result in scar formation. Human adult or fetal skin was placed subcutaneously in SCID mice and incisionally wounded. Wounds were excised after 4, 12, 24 or 72 h for IL-6 mRNA quantification by RT-PCR. In other grafts, 5 microgram of IL-6 was injected at wounding and then harvested at 7 days for analysis of scar formation. IL-6 production was examined in primary cultures of human fetal or adult dermal fibroblasts incubated for 8 h with 0, 0.1, 1 or 10 ng/ml of PDGF-BB. IL-6 mRNA was detected 4 h after wounding in fetal and adult wounds, but by 12 h there was no IL-6 mRNA in the fetal wounds. Adult wounds had IL-6 mRNA persisting to 72 h. IL-6 administration to fetal wounds resulted in scar formation. Fetal fibroblasts produced less IL-6 protein and mRNA at all points examined (P<0.01 vs adult). Diminished production of inflammatory cytokines such as IL-6 may be responsible for the lack of inflammation seen during fetal wound healing. Diminished inflammation may provide a permissive environment for scarless wound healing.
Liechty
K W
KW
Children's Institute for Surgical Science at The Children's Hospital of Philadelphia, The University of Pennsylvania School of Medicine, Philadelphia, PA, 19104, USA.
Adzick
N S
NS
Crombleholme
T M
TM
D000328:Adult; D000818:Animals; D000077214:Becaplermin; D002921:Cicatrix / Q000276:immunology* / Q000517:prevention & control; D016332:Fetal Tissue Transplantation / Q000502:physiology; D005347:Fibroblasts / Q000166:cytology / Q000276:immunology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics*; D007700:Kinetics; D051379:Mice; D016513:Mice, SCID; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger / Q000235:genetics; D012867:Skin / Q000166:cytology / Q000196:embryology / Q000276:immunology*; D016038:Skin Transplantation / Q000502:physiology*; D014158:Transcription, Genetic; D014183:Transplantation, Heterologous / Q000276:immunology / Q000502:physiology*; D014945:Wound Healing / Q000502:physiology*
D015850:Interleukin-6; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger; D000077214:Becaplermin