Department of Dermatology, Ruhr-University Bochum, Bochum, Germany.
Br J Dermatol. 2011 Jan;164(1):110-5. doi: 10.1111/j.1365-2133.2010.10099.x.
Current studies indicate that treatment with tumour necrosis factor (TNF)-α blockers plus ultraviolet (UV) B phototherapy results in higher relative Psoriasis Area and Severity Index reduction as compared with TNF-α monotherapy.
This study aimed to investigate the acute impact of etanercept on UVB-induced inflammation, cell cycle regulation and DNA damage.
Eleven subjects diagnosed with psoriasis who fulfilled the indication criteria for etanercept treatment were studied. A healthy skin site on the upper back was treated with UVB at 2 minimal erythema doses (MED). After 1, 24 and 72 h punch biopsies were taken from this site. Following the 72 h biopsy etanercept 50 mg was administered subcutaneously. After 48 h, 2 MED was given on healthy skin adjacent to previously treated skin sites. Again, after 1, 24 and 72 h punch biopsies were taken from this site. UVB- as well as UVB plus etanercept-treated skin was assessed by means of colorimetry and immunohistochemical studies for caspase 3, cyclin D(1), interleukin-12, Ki-67, p16, p53, survivin, thymine dimers and TNF-α.
Erythema formation did not differ significantly between UVB- and UVB plus etanercept-treated sites. Comparisons between UVB- and UVB plus etanercept-treated sites at a given time (1, 24, 72 h) did not result in significant differences in immunoreactivity of the markers investigated, except for cyclin D(1), p53 and survivin. Immunoreactivity of cyclin D(1) and p53 was significantly decreased in UVB plus etanercept-treated sites at 24 h. Survivin expression was significantly higher in UVB plus etanercept-treated skin as compared with UVB monotherapy.
Our data indicate that combined treatment with broadband UVB and TNF-α blockers might increase the risk of photocarcinogenesis by influencing apoptotic as well as antiapoptotic pathways.
目前的研究表明，与 TNF-α 单药治疗相比，肿瘤坏死因子（TNF）-α 阻滞剂联合紫外线（UV）B 光疗可使银屑病面积和严重程度指数（PASI）的相对缓解率更高。
本研究旨在探讨依那西普对 UVB 诱导的炎症、细胞周期调控和 DNA 损伤的急性影响。
研究了 11 名符合依那西普治疗适应证的银屑病患者。在背部上方的一个健康皮肤部位给予 2 个最小红斑剂量（MED）的 UVB 照射。在该部位分别于 1、24 和 72 小时进行皮肤活检。72 小时活检后，给予依那西普 50mg 皮下注射。48 小时后，在先前治疗的皮肤部位相邻的健康皮肤部位给予 2MED 的 UVB 照射。再次于 1、24 和 72 小时进行皮肤活检。采用比色法和免疫组织化学方法检测 UVB 以及 UVB 加依那西普治疗的皮肤中 caspase 3、细胞周期蛋白 D1（cyclin D1）、白细胞介素 12（IL-12）、Ki-67、p16、p53、survivin、胸腺嘧啶二聚体和 TNF-α。
UVB 与 UVB 加依那西普治疗的皮肤部位的红斑形成无显著差异。在给定时间（1、24、72 小时）对 UVB 与 UVB 加依那西普治疗的皮肤部位进行比较时，除 cyclin D1、p53 和 survivin 外，研究的标志物的免疫反应性无显著差异。UVB 加依那西普治疗的皮肤部位中 cyclin D1 和 p53 的免疫反应性在 24 小时时显著降低，而 survivin 的表达在 UVB 加依那西普治疗的皮肤中明显高于 UVB 单药治疗。
我们的数据表明，联合应用广谱 UVB 和 TNF-α 阻滞剂可能会通过影响凋亡和抗凋亡途径增加光致癌的风险。
