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 Citations (Scopus)

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

Fingerprint

Artificial Skin
Fibroblast Growth Factor 2
Interleukin-1
Nude Mice
Interleukin-6
Cytokines
Wounds and Injuries
Keratinocytes
Fibroblasts
Fibroblast Growth Factor 1
Glycosaminoglycans
Wound Healing
Cultured Cells
Intercellular Signaling Peptides and Proteins
Collagen
Enzyme-Linked Immunosorbent Assay
Immunohistochemistry
Serum

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

Cite this

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

In: Journal of Trauma - Injury, Infection and Critical Care, Vol. 40, No. 6, 06.1996, p. 894-899.

Research output: Contribution to journalArticle

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title = "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",
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.",
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T1 - 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

AU - Goretsky, Michael J.

AU - Harriger, M. Dana

AU - Supp, Andrew P.

AU - Greenhalgh, David G

AU - Boyce, Steven T.

PY - 1996/6

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N2 - 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.

AB - 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.

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