The effect of interferon-alpha-2b on wound contraction and scar contractures

Scar contraction following dermal injury is a leading cause of morbidity. The therapeutic use of interferon for fibroproliferative disorders has been suggested due to its antifibrotic properties. Assessment of the effect of interferon-{dollar}alpha{dollar}2b (IFN-{dollar}alpha{dollar}2b) on wound contraction was conducted within an in vitro model system, in vivo animal model, and by in situ analysis of human tissue. The fibroblast-populated collagen lattice (FPCL) simulates wound contraction. Using matched pairs of hypertrophic scar (HSc) and normal fibroblasts, exposure to IFN-{dollar}alpha{dollar}2b significantly inhibited contraction in a treatment time-dependent, serum sensitive manner. Comparison of HSc and normal fibroblasts revealed no significant differences in ability to induce contraction. Northern analysis revealed that IFN-{dollar}alpha{dollar}2b significantly down-regulated actin isoforms {dollar}beta{dollar} and {dollar}gamma{dollar}. FPCLs were stained with phalloidin which revealed morphologic alterations of the microfilaments following IFN-{dollar}alpha{dollar}2b treatment.; To establish the effect of IFN-{dollar}alpha{dollar}2b on contraction of full thickness wounds in vivo, osmotic pumps loaded with interferon or saline were implanted in guinea pigs. Seven days later full thickness wounds were created. Comparisons indicated a significant reduction in wound contraction in the treated animals. Immunochemical analysis of the tissue indicated that although the relative amount of vimentin was increased after wounding, the myofibroblast-associated cytoskeletal proteins were not. Immunohistochemistry localized the expression of {dollar}alpha{dollar}-smooth muscle actin ({dollar}alpha{dollar}-SMA) and lack of decorin, within the central region of the 21 day wound of the treated animal. Localization of apoptotic cells revealed an increase in the treated animal but this could not be localized to {dollar}alpha{dollar}-SMA staining.; The expression of {dollar}alpha{dollar}-SMA was quantitated in human burn wounds, HSc, normal scar and normal tissue. The percentage of myofibroblasts was significantly higher within HSc relative to normal scar or normal tissue. Staining for {dollar}alpha{dollar}-SMA was most intense in regions where abnormal collagen fibrils were present. The presence of myofibroblasts did not correlate with the severity of HSc. The total number of fibroblasts was twice that in normal tissue. Tissue sections obtained from patients who had received systemic IFN-{dollar}alpha{dollar}2b showed a reduction in myofibroblasts and total number of fibroblasts and an increased number of apoptotic cells.