Myofibroblasts and apoptosis in human hypertrophic scars: the effect of interferon-alpha2b.
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-alpha2b 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-alpha2b and had biopsy material taken before, during, and after IFN therapy. The tissue was analyzed by immunohistochemical staining for alpha-smooth muscle actin (alpha-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 alpha-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-alpha2b 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-alpha2b may contribute to the resolution of HSc in part by the enhanced induction of apoptosis.
Nedelec
B
B
Department of Surgery, University of Alberta, Edmonton, Alberta, Canada.
Shankowsky
H
H
Scott
P G
PG
Ghahary
A
A
Tredget
E E
EE
D000199:Actins / Q000032:analysis; D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000187:drug effects*; D002056:Burns / Q000150:complications*; D002452:Cell Count; D017439:Cicatrix, Hypertrophic / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D006801:Humans; D020287:In Situ Nick-End Labeling; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011994:Recombinant Proteins
D000199:Actins; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins