Lerche Catharina M, Philipsen Peter A, Poulsen Thomas, Wulf Hans Christian
Department of Dermatology, Copenhagen University Hospital, Bispebjerg, Copenhagen, Denmark.
Exp Dermatol. 2008 Jan;17(1):57-62. doi: 10.1111/j.1600-0625.2007.00617.x.
Numerous studies have demonstrated the utility of topical tacrolimus ointment in atopic dermatitis. However, there is a concern that local immunosuppression by calcineurin inhibitors may enhance dermal photocarcinogenesis and carcinogenesis. Therefore, we investigated the influence of topical tacrolimus ointment on squamous cell carcinoma formation in hairless female C3.Cg/TifBomTac immunocompetent mice exposed to solar simulated radiation (SSR). In a first experiment, mice (n = 200) had tacrolimus applied on their dorsal skin three times weekly followed by SSR (2, 4 or 6 standard erythema doses, SED) 3-4 h later. Tacrolimus did not reduce the time to tumor development and in the group receiving 4 SED it even had a protective effect (156 days vs 170 days, P = 0.008). In a second experiment, mice (n = 50) were irradiated with 6 SED three times weekly for 3 months and subsequently treated five times weekly with topical tacrolimus to mimic the use of tacrolimus on sun-damaged skin. The median time to the first skin tumor was 234 days in SSR + tacrolimus group compared with 227 days in the only SSR-irradiated group (P = 0.160). In a third experiment, mice (n = 25) had tacrolimus applied on their dorsal skin every day for 1 month, thereafter the group was irradiated with 4 SED three times weekly. The median time to the first skin tumor was 142 days in tacrolimus + SSR group compared with 156 days in the only SSR-irradiated group from experiment 1 (P = 0.363). We conclude that tacrolimus ointment does not accelerate photocarcinogenesis or induce any dermal carcinogenicity in hairless mice.
众多研究已证实局部用他克莫司软膏在特应性皮炎治疗中的效用。然而，人们担心钙调神经磷酸酶抑制剂引起的局部免疫抑制可能会增强皮肤光致癌作用和致癌作用。因此，我们研究了局部用他克莫司软膏对暴露于模拟太阳辐射（SSR）的无毛雌性C3.Cg/TifBomTac免疫活性小鼠鳞状细胞癌形成的影响。在第一个实验中，每周3次在小鼠（n = 200）背部皮肤涂抹他克莫司，3 - 4小时后给予SSR（2、4或6个标准红斑剂量，SED）。他克莫司并未缩短肿瘤发生时间，在接受4个SED的组中甚至具有保护作用（156天对170天，P = 0.008）。在第二个实验中，每周3次对小鼠（n = 50）照射6个SED，持续3个月，随后每周5次局部用他克莫司治疗，以模拟在晒伤皮肤上使用他克莫司的情况。SSR + 他克莫司组出现首个皮肤肿瘤的中位时间为234天，而仅接受SSR照射的组为227天（P = 0.160）。在第三个实验中，每天在小鼠（n = 25）背部皮肤涂抹他克莫司，持续1个月，此后该组每周3次接受4个SED照射。他克莫司 + SSR组出现首个皮肤肿瘤的中位时间为142天，相比实验1中仅接受SSR照射的组的156天（P = 0.363）。我们得出结论，他克莫司软膏不会加速无毛小鼠的光致癌作用，也不会诱发任何皮肤致癌性。
