Myofibroblasts and apoptosis in human hypertrophic scars: The effect of interferon-alpha 2b

Background. Hypertrophic scars (HSc) are a dermal fibroproliferative disord er 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 heat without the d evelopment of HSc (normotrophic scars), (2) to examine the presence of myof ibroblasts and apoptosis in normotrophic and HSc scars over time, and (3) t o determine if the systemic administration of IFN-alpha 2b can induce apopt osis. Methods. Two groups of patients underwent serial tissue biopsies. Six burn patients were studied prospectively by, obtaining biopsy specimens from wou nd granulation tissue, normal skin, post-burn Hsc, and normotrophic scars ( heated donor sites). A second patient group with HSc was treated with syste mic IFN-alpha 2b and had biopsy material taken before, during, and after IF N therapy. The tissue was analyzed by immunohistochemical staining for alph a -smooth muscle actin (alpha -SMA) and in situ DNA fragmentation terminal deoxynucleolidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) assay for apoptosis. Results. The total numbers of fibroblasts in HSc were found to be similar t o granulation tissue and twice that of normal skin and normotrophic scar. O ver time the numbers of cells in HSc tissue decreased toward normal skin le vels. There was a significantly higher percentage oof fibroblasts staining for alpha -SMA in HSc as compared with normotrophic scar or normal skin obt ained from the same patient (P > .05). Serial biopsy specimens of resolving HSc tissue obtained from the patients who received systemic IFN-alpha 2b s howed a general reduction in total number of fibroblasts and myofibroblasts associated with a significant increase in the Percentage of apoptotic cell s compared with normal dermis from the same Patient. Conclusions. HSc tissues have greater numbers of fibroblasts and myofibrobl asts than normal skin and normotrophic scars. As HSc remodels, the numbers of fibroblasts and myofibroblasts reduces, possibly by the induction of apo plosis. Systemic IFN-alpha 2b may contribute to the resolution of HSc in pa rt by the enhanced induction of apoplosis.