Abstract
Interferons (IFN), including IFN-alpha 2b, have been used as antifibrogenic factors to modulate the excessive production of extracellular matrix (ECM) associated with dermal fibroproliferative disorders. This study was conducted to examine the ability of a dermal cream containing liposome-encapsulated IFN-alpha 2b (LIPO+IFN) to affect the synthesis of ECM in open and reepithelialized wounds. Full-thickness skin wounds in 32 female Hartley guinea pigs (6 wounds per animal, 3 on each side) were made with an 8-mm biopsy punch. Each wound on the right side received 3000 U LIPO+IFN, whereas wounds on the left side received cream containing empty liposomes. Histologic examination revealed a significant reduction in scar formation in LIPO+IFN-treated but not in vehicle-treated wounds. Northern analysis showed reductions in type I procollagen mRNA in healed wounds treated with LIPO+IFN (day 4 groups: 1596.9+/-207 vs. 3710.2+/-493 densitometry units, p < 0.01, n=8). This was consistent with a reduction in the concentration of collagen in the tissue, assayed as 4-hydroxyproline (day 4 group: 38.5+/-3.8 vs. 54.5+/-3.9 mu g per tissue, p < 0.01, n=8). Even when applied to reepithelialized wounds, LIPO+IFN caused a marked reduction in type I collagen mRNA (1938.5+/-579 vs. 4085.7+/-1271 densitometry units, p < 0.01, n=8). These findings support the concept of the early topical use of this antifibrogenic agent for treatment of dermal fibroproliferative disorders, such as hypertrophic scars.
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