Applied Pharmacology Research Laboratories, Drug Discovery Research, Astellas Pharmaceutical Inc, Tsukuba, Ibaraki, Japan.
Arch Dermatol Res. 2010 Nov;302(9):645-52. doi: 10.1007/s00403-010-1056-1. Epub 2010 Jun 13.
Topical glucocorticoids, widely used for the treatment of a variety of dermatitises, are known to exacerbate atopic dermatitis after long-term or inappropriate use. In some animal models, topical glucocorticoids augment the allergic cutaneous inflammation after repeated application, suggesting a relationship between these and clinical observations. We investigated whether topical glucocorticoids augment itching, rather than inflammation, resulting in the exacerbation of atopic dermatitis. Mice receiving repeated topical application of glucocorticoids, betamethasone valerate or dexamethasone, to the ear for 1 week showed significantly higher scratching frequency after application of an irritant chemical, 2,4-dinitrofluorobenzene (DNFB) or 12-O-tetradecanoilphorbol 13-acetate (TPA) than those receiving either a glucocorticoid or irritant chemical alone. In contrast, the increase in ear thickness induced by application of TPA was significantly suppressed by dexamethasone. Substance P (SP) and nerve growth factor (NGF) levels were higher in the ear receiving betamethasone valerate followed by DNFB application than in that receiving DNFB alone. In addition, histopathological studies revealed an increased density of nerve fibers in the ear receiving betamethasone valerate or dexamethasone followed by DNFB application. Oral administration of betamethasone valerate was not associated with an increase in either scratching frequency or SP or NGF level in the ear. These results suggest that repeated topical application of glucocorticoids may augment irritant chemical-triggered scratching through an increase in SP and NGF levels and nerve fiber density at the application site. These findings might explain the etiology of the exacerbation of atopic dermatitis and other dermatitises, occurring after long-term or inappropriate use of topical glucocorticoids.
局部糖皮质激素广泛用于治疗各种皮炎，已知长期或不当使用会加重特应性皮炎。在一些动物模型中，局部糖皮质激素在反复应用后会增强过敏性皮肤炎症，这表明它们与临床观察之间存在关系。我们研究了局部糖皮质激素是否会增强瘙痒而不是炎症，从而导致特应性皮炎恶化。接受反复局部应用糖皮质激素（倍他米松戊酸酯或地塞米松）治疗 1 周的小鼠，在应用刺激性化学物质 2,4-二硝基氟苯（DNFB）或 12-O-十四烷酰佛波醇 13-乙酸酯（TPA）后，搔抓频率明显高于仅接受糖皮质激素或刺激性化学物质的小鼠。相比之下，应用 TPA 后耳厚度的增加明显被地塞米松抑制。应用倍他米松戊酸酯后再应用 DNFB 会导致耳中 P 物质（SP）和神经生长因子（NGF）水平升高，高于仅应用 DNFB 的水平。此外，组织病理学研究显示，在应用倍他米松戊酸酯或地塞米松后再应用 DNFB 的耳朵中，神经纤维密度增加。口服倍他米松戊酸酯不会导致搔抓频率、SP 或 NGF 水平在耳朵中的增加。这些结果表明，反复局部应用糖皮质激素可能通过增加刺激性化学物质触发搔抓的 SP 和 NGF 水平以及应用部位的神经纤维密度来加剧。这些发现可能解释了长期或不当使用局部糖皮质激素后特应性皮炎和其他皮炎恶化的病因。
