Petzelbauer P, Wolff K
Department of Dermatology 1, Vienna Medical School, Austria.
Br J Dermatol. 1992 Dec;127(6):560-5. doi: 10.1111/j.1365-2133.1992.tb14865.x.
Cyclosporin A (CyA) has proved effective in various dermatological diseases, but its mechanisms of action within the skin are still ill-defined. In order to characterize more clearly the cellular targets of CyA we examined its effects on skin immune cells in normal and UVB- and PUVA-irradiated skin by means of a three-step immunoperoxidase reaction and immunofluorescence double-labelling technique. The CyA-induced depletion of epidermal Langerhans cells equals that seen with UVB or PUVA alone. CyA alone has no effect on the number and distribution of dermal cells. CyA modulates the UV irradiation-induced changes by: (i) inhibiting the UVB- and PUVA-induced ICAM-1 expression by keratinocytes and (ii) suppressing the PUVA-induced upregulation of CD11a expression by macrophages (72 +/- 12% of Ki-M8+ macrophages express CD11a with PUVA, compared with 20 +/- 5% with CyA + PUVA, P < 0.001). Neither treatment affected ICAM-1 expression by endothelial cells. In addition, CyA increases PUVA minimal phototoxicity dose from 10 +/- 2.6 J/cm2 (PUVA alone) to 15.3 +/- 3.1 J/cm2 (CyA + PUVA), (P < 0.001). In conclusion, the effects of CyA on the skin include a down-modulation of the PUVA-erythema reaction, associated with a direct or indirect modulation of adhesion molecule expression.
环孢素A（CyA）已被证明对多种皮肤病有效，但其在皮肤内的作用机制仍不明确。为了更清楚地表征CyA的细胞靶点，我们通过三步免疫过氧化物酶反应和免疫荧光双标记技术，研究了其对正常皮肤以及紫外线B（UVB）和补骨脂素加长波紫外线（PUVA）照射皮肤中免疫细胞的影响。CyA诱导的表皮朗格汉斯细胞耗竭与单独使用UVB或PUVA时相当。单独使用CyA对真皮细胞的数量和分布没有影响。CyA通过以下方式调节紫外线照射引起的变化：（i）抑制角质形成细胞中UVB和PUVA诱导的细胞间黏附分子-1（ICAM-1）表达；（ii）抑制巨噬细胞中PUVA诱导的CD11a表达上调（PUVA处理时，72±12%的Ki-M8+巨噬细胞表达CD11a，而CyA + PUVA处理时为20±5%，P<0.001）。两种处理均未影响内皮细胞的ICAM-1表达。此外，CyA将PUVA的最小光毒性剂量从10±2.6 J/cm²（单独使用PUVA）增加到15.3±3.1 J/cm²（CyA + PUVA），（P<0.001）。总之，CyA对皮肤的作用包括下调PUVA红斑反应，这与黏附分子表达的直接或间接调节有关。
