Involution of keloid implants in athymic mice treated with pirfenidone or with triamcinolone

The experimental drug pirfenidone (PFD) has been evaluated as an inhibitor of keloid proliferation and compared with triamcinolone (TAC) injections by studying the involution of active human keloid implants in athymic nude mice (nu-nu). PFD was fed to mice with keloid implants at a level of 2.75 mg/g of feed. At this level PFD had no adverse effect on the body weights of the mice. Implant weights in both PFD-fed and control mice decreased with time. The weights of the implants from the PFD group were significantly lower than those of the control implants at 60 and 90 days after implantation. Consequently PFD may cause an increased degradation and absorption of keloid tissue. The implants from the PFD mice were not significantly different histologically from the implants of the mice with corresponding implants. The chondroitin-4-sulfate (C4S) levels of the implants from PFD-fed mice were not significantly different from those of the implants from control mice. Therefore the mechanism of action of PFD apparently is not mediated by an effect on C4S metabolism. In contrast, the injections of TAC at a level that caused temporary body weight loss in the mice resulted in significant decreases in both hyaluronic acid (HA) and C4S in the keloid implants. Histologically, fibroblasts disappeared from the implants treated with TAC by 20 days after injection. At 30 days after TAC injection, HA and C4S were not detected by electrophoresis in keloid implants; only dermatan sulfate appeared to be present.