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银屑病患者在环孢素A治疗期间未受累皮肤对反复胶带剥离的反应。

Response of the clinically uninvolved skin of psoriatic patients to repeated tape stripping during cyclosporin A treatment.

作者信息

Gerritsen M J, Rulo H F, Arnold W P, Van de Kerkhof P C

机构信息

Department of Dermatology, University Hospital Nijmegen, The Netherlands.

出版信息

Br J Dermatol. 1994 Feb;130(2):181-8. doi: 10.1111/j.1365-2133.1994.tb02897.x.

Abstract

It is well established that cyclosporin A (CyA), a widely used immunosuppressant in human organ transplantation, is an effective drug in the treatment of psoriasis. Although it has been postulated that the effect of CyA in psoriasis is mediated through antilymphocyte activity, there is also evidence suggesting that CyA exerts a direct cytostatic effect on epidermal keratinocytes, but results of studies relating to the latter have been contradictory. Using immunohistochemical methods we investigated the influence of systemic CyA on proliferation and differentiation in the tape-stripped uninvolved skin of psoriatic patients, a model which provides the opportunity of studying epidermal regeneration in the absence of a significant accumulation of T lymphocytes. We addressed the question of whether CyA (3-5 mg/kg/day) modulates epidermal proliferation and differentiation following standardized injury in uninvolved skin of psoriatic patients. Ten patients with severe psoriasis participated in this study. The dosages of CyA were sufficient to induce a marked and statistically significant improvement (PASI, week 0, 20.5 +/- 4.4; PASI, week 16, 4.3 +/- 0.6). Before CyA treatment, and during week 16 of treatment, Sellotape stripping was carried out on a 2-cm2 area of the uninvolved skin of psoriatic patients. After 48 h punch biopsies were taken. Immunohistochemical assessment of recruitment of cycling cells (Ki-67), filaggrin, involucrin, T lymphocytes and tenascin, was carried out. We did not find any significant alteration during the treatment period in the tape-stripped uninvolved skin of psoriatic patients. We conclude that epidermal hyperproliferation and abnormal keratinization are not modulated directly by CyA at therapeutic doses in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)

摘要

众所周知,环孢素A(CyA)是一种在人体器官移植中广泛使用的免疫抑制剂,也是治疗银屑病的有效药物。尽管有人推测CyA对银屑病的作用是通过抗淋巴细胞活性介导的,但也有证据表明CyA对表皮角质形成细胞具有直接的细胞抑制作用,但相关研究结果相互矛盾。我们采用免疫组织化学方法,研究了全身性CyA对银屑病患者未受累皮肤胶带剥离后增殖和分化的影响,该模型为在T淋巴细胞无明显积聚的情况下研究表皮再生提供了机会。我们探讨了CyA(3 - 5mg/kg/天)是否能调节银屑病患者未受累皮肤标准化损伤后的表皮增殖和分化这一问题。10名重度银屑病患者参与了本研究。CyA的剂量足以诱导显著且具有统计学意义的改善(银屑病面积和严重程度指数,第0周,20.5±4.4;第16周,4.3±0.6)。在CyA治疗前以及治疗的第16周,对银屑病患者未受累皮肤2平方厘米区域进行胶带剥离。48小时后进行打孔活检。对循环细胞(Ki - 67)、丝聚合蛋白、兜甲蛋白、T淋巴细胞和腱生蛋白的募集进行免疫组织化学评估。我们未发现银屑病患者胶带剥离的未受累皮肤在治疗期间有任何显著变化。我们得出结论,在体内治疗剂量下,CyA不会直接调节表皮过度增殖和异常角化。(摘要截断于250字)

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