Department of Oncology, University Hospital Zurich, Wagistrasse 14, 8952 Schlieren, Switzerland.
Nat Commun. 2013;4:1560. doi: 10.1038/ncomms2566.
Aldara is a cream used for topical treatment of non-melanoma skin cancer, and is thought to act through stimulation of anti-tumour immunity. The active ingredient, imiquimod, has been shown to stimulate toll-like receptor 7. Aldara also induces psoriasis-like lesions when applied to naive murine skin, and as such is used as a mouse model for psoriasis. Here we find that in naive murine skin, Aldara induces inflammation largely independently of toll-like receptor 7. Surprisingly, inflammasome activation, keratinocyte death and interleukin 1 release also occur in response to the vehicle cream in the absence of imiquimod. We show that isostearic acid, a major component of the vehicle, promotes inflammasome activation in cultured keratinocytes, and so may contribute to the observed effects of Aldara on murine skin. Aldara therefore stimulates at least two immune pathways independently, and both imiquimod and vehicle are required for a full inflammatory response. Although it remains to be tested, it is possible that imiquimod-independent effects also contribute to the therapeutic efficacy of Aldara.
Aldara 是一种用于治疗非黑色素瘤皮肤癌的乳膏，被认为通过刺激抗肿瘤免疫起作用。其活性成分咪喹莫特已被证明可刺激 Toll 样受体 7。当 Aldara 应用于未致敏的鼠皮肤时，会诱导出类似银屑病的病变，因此被用作银屑病的小鼠模型。在这里，我们发现 Aldara 在未致敏的鼠皮肤中诱导炎症在很大程度上独立于 Toll 样受体 7。令人惊讶的是，在没有咪喹莫特的情况下，炎症小体的激活、角质形成细胞的死亡和白细胞介素 1 的释放也会发生在载体乳膏中。我们表明，异硬脂酸是载体的主要成分之一，可促进培养角质形成细胞中的炎症小体激活，因此可能导致 Aldara 对鼠皮肤产生观察到的影响。因此，Aldara 至少独立地刺激了两种免疫途径，并且需要咪喹莫特和载体才能产生完整的炎症反应。虽然还有待测试，但 Aldara 治疗效果的独立于咪喹莫特的作用可能也有贡献。
