The antifibrogenic effects of liposome-encapsulated IFN-alpha2b cream on skin wounds.
Interferons (IFN), including IFN-alpha2b, 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-alpha2b (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 3,000 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 microg 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.
Takeuchi
M
M
Department of Plastic and Reconstructive Surgery, School of Medicine, Tokyo Women's Medical University, Japan.
Tredget
E E
EE
Scott
P G
PG
Kilani
R T
RT
Ghahary
A
A
D000818:Animals; D002921:Cicatrix / Q000517:prevention & control; D004304:Dosage Forms; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005355:Fibrosis; D006168:Guinea Pigs; D006909:Hydroxyproline / Q000378:metabolism; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage*; D008081:Liposomes; D011347:Procollagen / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins; D012867:Skin / Q000187:drug effects* / Q000293:injuries* / Q000473:pathology
D004304:Dosage Forms; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D008081:Liposomes; D011347:Procollagen; D012333:RNA, Messenger; D011994:Recombinant Proteins; D006909:Hydroxyproline