薬理と治療

Abstract

Objectives We have encountered several cases in which the symptoms of keloid improvedthrough the concomitant internal use of itraconazole（ITCZ）, which is an antifungal agent, forcomplications of trichophytosis. These cases suggest the possibility that fungi may beinvolved in keloid formation and, at the same time, it is believed that the effects of ITCZ onkeloid should also be evaluated.In this study, we focused on the antiangiogenic properties of ITCZ and studied theeffects of ITCZ on the vascular endothelial growth factor（VEGF）production of culturedkeloid fibroblasts.Methods Using six specimens of normal skin and nine keloid specimens obtained duringsurgery, the fibroblasts of each specimen were cultured according to a common method.Using the normal−skin−derived fibroblasts（NSF）and the keloid−derived fibroblasts（KF）,a control group in which only the 100％ dimethyl sulfoxide（DMSO）was added and groups inwhich ITCZ at concentrations of 0.5μg／mL and 1.0μg／mL were added were further culturedfor 24 hours. Supernatant was collected and the VEGF were measured using the EIA（enzyme immunoassay）method.Results In a comparison using the control group, the production of VEGF significantlyincreased in KF in comparison to NSF. In the comparison of KF with the control group, no differenceswere observed based on the concentration, but a significant inhibition of VEGF productionwas observed with the addition of ITCZ.Conclusions In the results of this study, ITCZ inhibited the VEGF production of keloidfibroblasts, thus indicating the possibility that ITCZ may have had some effect on the keloids.It is believed that a new approach to keloids which are regarded as intractable can beexpected by elucidate many issues, such as the mechanism of action of antifungal agent onkeloids.（Jpn Pharmacol Ther 2009；37：753−6）KEY WORDS Itraconazole（ITCZ）, Keloid, Fibroblasts, VEGF（vascular endothelial growthfactor）