Expression of Interleukin-1α, Interleukin-6, and Basic Fibroblast Growth Factor by Cultured Skin Substitutes before and after Grafting to Full-Thickness Wounds in Athymic Mice

Michael J. Goretsky, M. Dana Harriger, Andrew P. Supp, David G Greenhalgh, Steven T. Boyce

Research output: Contribution to journalArticle

38 Scopus citations

Abstract

Objectives: Cultured skin substitutes (CSSs), consisting of human keratinocytes and human fibroblasts attached to collagen-glycosaminoglycan substrates, have been demonstrated to cover wounds, and may release detectable quantities of growth factors that promote wound healing. Materials and Methods: Basic fibroblast growth factor (bFGF), interleukin-1α (IL-1α), and interleukin-6 (IL-6) were assayed by enzyme linked immunosorbent assay and immunohistochemistry in CSSs in vitro and at days 1, 3, 7, 14, and 21 after grafting to full-thickness wounds in athymic mice. Measurements and Main Results: When isolated cells were tested, IL-1α was found to come primarily from the keratinocytes, whereas bFGF was from the fibroblasts. Combinations of both cell types in the CSSs resulted in a synergistic enhancement of IL-6 expression. Quantities of all three cytokines from CSSs were greater in vitro compared with in vivo levels at all time points after grafting. bFGF increased from day 1 to day 7, and then remained relatively constant until day 21. At day 3 maximal levels of IL-1α were observed. By day 7, IL-1α decreased to approximately 40% of maximal levels, and subsequently increased until day 21. IL-6 levels were highest at day 7 after grafting. All cytokines had reached elevated levels during the time of wound revascularization (days 3-7). Conclusions: The sequence of cytokine synthesis in the wounds (i.e., rapid IL-1α increase followed by IL-6 expression) parallels serum levels reported after a septic challenge. These findings support the hypothesis that the wound is a source of systemic cytokines.

Original languageEnglish (US)
Pages (from-to)894-899
Number of pages6
JournalJournal of Trauma - Injury, Infection and Critical Care
Volume40
Issue number6
StatePublished - Jun 1996
Externally publishedYes

Keywords

  • Basic fibroblast growth factor
  • Collagen-glycosaminoglycan
  • Cultured skin substitute
  • Human fibroblasts
  • Human keratinocytes
  • Interleukin-1α
  • Interleukin-6
  • Split thickness autografts

ASJC Scopus subject areas

  • Surgery

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