A. KONDO1, M. Aoki1, N. Matsunaga1, A. Honda1, Y. Okubo1, R. Ogawa1 1Nippon Medical School,Plastic, Reconstructive, And Aesthetic Surgery,Bunkyo, TOKYO, Japan
Background:Keloids and hypertrophic scars (HSs) are excessive scar formations with chronic inflammation and capillary vasculogenesis. Keloids, in particular, are refractory as they are resistant to treatments including steroids. Fingolimod (FTY 720) is an analog of sphingosine-1-phosphate (S1P). S1P is a lipid mediator, which is involved in inflammatory cell recruitment and angiogenesis. FTY720 is a functional antagonist of S1P receptor 1 (S1PR1), and inhibits sphingosine kinase 1 (SphK1), which produces S1P. We hypothesized that topical application of FTY720 would decrease inflammatory cells in the local region, and inhibit angiogenesis. We examined the effects of topical FTY720 injection on mechanical force-induced scarring.
Methods: C57BL6/J mice (8 weeks of age, male) were used. VECTOR 620 expansion screws (SCHEU, Iserlohn, Germany) were used for biomechanical loading. Two-cm linear full-thickness incisions were made on the dorsum of the mouse and then sutured with 4–0 vicryl. On day 6, the vicryl sutures were removed and loading devices were secured with 5–0 nylon sutures, and mechanical force was applied. On days 8, 10, and 12, intra-cutaneous FTY720 (10μM) or control injections were performed, and the tension on the scar was reapplied. On day 14, the tissues were harvested for analysis.
Results:Compared to the control group, reduction of the scar was observed in the FTY720 group. Histological analysis showed that the size of scar area was significantly decreased in the FTY720 group compared to the control group. Further, CD34 immunostaining was performed and the number of capillary vessels was counted. Significant increase in the number of blood vessels was observed in the FTY720 group compared to the control group. No significant difference was observed in the blood lymphocyte fraction.
Conclusions:FTY720 acts with a unique mechanism that differs from conventional immunosuppressive agents. Topical application of FTY720 is expected to be effective for various inflammatory and allergic diseases and may be a novel therapeutic agent for treating keloids/HSs.