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布地奈德局部治疗对银屑病表皮增殖、角化和炎症参数的影响。

Effects of topical treatment with budesonide on parameters for epidermal proliferation, keratinization and inflammation in psoriasis.

作者信息

de Jong E M, Ferrier C M, de Zwart A, Wauben-Penris P J, Korstanje C, van de Kerkhof P C

机构信息

Department of Dermatology, University Hospital Nijmegen, The Netherlands.

出版信息

J Dermatol Sci. 1995 May;9(3):185-94. doi: 10.1016/0923-1811(94)00376-p.

DOI:10.1016/0923-1811(94)00376-p
PMID:8664216
Abstract

Corticosteroids are important in the treatment of inflammatory dermatoses, such as psoriasis. They have anti-inflammatory, anti-proliferative and immunosuppressive effects. In this study, the effect of budesonide on proliferation, inflammatory cells and cytokines in psoriasis was investigated. In order to elucidate the time course of the different effects of corticosteroid treatment in psoriasis, six patients were treated for 3 weeks with budesonide 0.025% ointment (Preferid), and biopsies were studied immunohistochemically, before treatment and after 1 and 3 weeks of treatment. Clinical scores together with staining with antibodies indicating proliferation, keratin 16, keratin 10, T-lymphocytes, monocytes, polymorphonuclear leukocytes, Langerhans cells, interleukin-1alpha (IL-1alpha), interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-alpha (TNF-alpha), and intercellular adhesion molecule-1 (ICAM-1) were performed. 'Psoriasis area' and 'severity index' (PASI) scores were significantly reduced after 1 week and 3 weeks of treatment. Epidermal hyperproliferation (Ki-67 binding) and suprabasal keratin 16 (Ks8.12) expression decreased within 1 week, while keratin 10 (RKSE60) expression did not change. Five out of 6 patients showed cytokine levels (IL-1alpha, IL-6, IL-8, and TNF-alpha; detected immunohistochemically) in the normal range, while 1 patient had highly increased cytokine levels. In this patient, cytokine levels decreased during treatment. In 4 patients, showing high dermal ICAM-1 expression before treatment, a consistent reduction of ICAM-1 on endothelial cells was observed. The inflammatory infiltrate (T-lymphocytes (T11), monocytes/macrophages (WT14), polymorphonuclear leukocytes (PMN, anti-elastase)) was reduced to some extent after 3 weeks. The number of Langerhans cells (OKT6) did not change. These results indicate that the psoriatic lesions, although clinically comparable, show interindividual differences in cytokine expression. Corticosteroid treatment for 1-3 weeks improves clinical scores and hyperproliferation. Cytokine levels are reduced during steroid treatment in the patient who showed high levels before treatment. To suppress the infiltrate entirely, longer steroid treatment is probably necessary. This may explain the relapse seen after short term corticosteroid therapy.

摘要

皮质类固醇在治疗炎症性皮肤病(如银屑病)中具有重要作用。它们具有抗炎、抗增殖和免疫抑制作用。在本研究中,调查了布地奈德对银屑病中细胞增殖、炎症细胞和细胞因子的影响。为了阐明皮质类固醇治疗银屑病不同作用的时间进程,6例患者使用0.025%布地奈德软膏(普米克令舒)治疗3周,在治疗前、治疗1周和3周后进行活检,并进行免疫组织化学研究。同时进行临床评分以及用指示增殖的抗体、角蛋白16、角蛋白10、T淋巴细胞、单核细胞、多形核白细胞、朗格汉斯细胞、白细胞介素-1α(IL-1α)、白细胞介素-6(IL-6)、白细胞介素-8(IL-8)、肿瘤坏死因子-α(TNF-α)和细胞间黏附分子-1(ICAM-1)进行染色。治疗1周和3周后,“银屑病面积”和“严重程度指数”(PASI)评分显著降低。表皮过度增殖(Ki-67结合)和基底层上角蛋白16(Ks8.12)表达在1周内下降,而角蛋白10(RKSE60)表达未改变。6例患者中有5例细胞因子水平(IL-1α、IL-6、IL-8和TNF-α;免疫组织化学检测)在正常范围内,而1例患者细胞因子水平大幅升高。在该患者中,细胞因子水平在治疗期间下降。在4例治疗前显示真皮ICAM-1高表达的患者中,观察到内皮细胞上ICAM-1持续减少。3周后炎症浸润(T淋巴细胞(T11)、单核细胞/巨噬细胞(WT14)、多形核白细胞(PMN,抗弹性蛋白酶))在一定程度上减少。朗格汉斯细胞(OKT6)数量未改变。这些结果表明,银屑病皮损尽管在临床上具有可比性,但在细胞因子表达上存在个体差异。皮质类固醇治疗1 - 3周可改善临床评分和过度增殖。在治疗前细胞因子水平较高的患者中,类固醇治疗期间细胞因子水平降低。为了完全抑制浸润,可能需要更长时间的类固醇治疗。这可能解释了短期皮质类固醇治疗后出现的复发现象。

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