Abstract
Background. Hypertrophic scars (HSc) are a dermal fibroproliferative disorder that leads to considerable
morbidity. Preliminary evidence suggests that interferon (IFN) may improve HSc clinically.
The aims of this study were (1) to compare the cell density in HSc and in wounds that
heal without the development of HSc (normotrophic scars), (2) to examine the presence
of myofibroblasts and apoptosis in normotrophic and HSc scars over time, and (3) to
determine if the systemic administration of IFN-α2b can induce apoptosis. Methods. Two groups of patients underwent serial tissue biopsies. Six burn patients were studied
prospectively by obtaining biopsy specimens from wound granulation tissue, normal
skin, post-burn HSc, and normotrophic scars (healed donor sites). A second patient
group with HSc was treated with systemic IFN-α2b and had biopsy material taken before,
during, and after IFN therapy. The tissue was analyzed by immunohistochemical staining
for α-smooth muscle actin (α-SMA) and in situ DNA fragmentation terminal deoxynucleotidyl
transferase-mediated dUTP-biotin nick end labeling (TUNEL) assay for apoptosis. Results. The total numbers of fibroblasts in HSc were found to be similar to granulation tissue
and twice that of normal skin and normotrophic scar. Over time the numbers of cells
in HSc tissue decreased toward normal skin levels. There was a significantly higher
percentage of fibroblasts staining for α-SMA in HSc as compared with normotrophic
scar or normal skin obtained from the same patient (P >.05). Serial biopsy specimens of resolving HSc tissue obtained from the patients
who received systemic IFN-α2b showed a general reduction in total number of fibroblasts
and myofibroblasts associated with a significant increase in the percentage of apoptotic
cells compared with normal dermis from the same patient. Conclusions. HSc tissues have greater numbers of fibroblasts and myofibroblasts than normal skin
and normotrophic scars. As HSc remodels, the numbers of fibroblasts and myofibroblasts
reduces, possibly by the induction of apoptosis. Systemic IFN-α2b may contribute to
the resolution of HSc in part by the enhanced induction of apoptosis. (Surgery 2001;130:798-808.)
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Article info
Publication history
Accepted:
April 7,
2001
Footnotes
*Supported by the Firefighters' Burn Trust Fund of the University of Alberta Hospitals, the Harold and Emilie Tucker Trust Fund of the University of Alberta Hospitals (B.N.), Alberta Heritage Foundation for Medical Research (E.E.T., Scholar), and the Medical Research Council of Canada (P.G.S., A.G., E.E.T.).
**Reprint requests: Edward E. Tredget, MD, MSc, FRCSC, 2D3.81 WMHCS, University of Alberta Hospital, 8440-112 St, Edmonton, Alberta, Canada T6G 2B7.
Identification
Copyright
© 2001 Mosby, Inc. Published by Elsevier Inc. All rights reserved.
