Ooi T, Barnetson R Stc, Zhuang L, McKane S, Lee J H, Slade H B, Halliday G M
Department of Dermatology, Melanoma and Skin Cancer Research Institute, University of Sydney at Royal Prince Alfred Hospital, Camperdown, NSW 2050, Australia.
Br J Dermatol. 2006 Jan;154(1):72-8. doi: 10.1111/j.1365-2133.2005.06932.x.
Imiquimod 5% cream is a topically applied immune response modifier that has been shown to give effective treatment of actinic keratosis (AK). The therapeutic effects of imiquimod are likely to involve the provocation of a cutaneous immune response against abnormal cells, an assumption based on a strong correlation between complete clearance rates and the severity of the local skin reactions (erythema, oedema, erosion/ulceration, weeping/exudation and scabbing/crusting); however, no clinical studies have conclusively proved this mechanism.
To determine the nature of cellular infiltrates induced by the application of imiquimod to AK lesions and to study cells involved in the cutaneous immune response.
Eighteen patients participated in this phase I, randomized, double-blind, parallel group, vehicle-controlled study. Enrolled patients were randomized in a 2 : 1 ratio to receive imiquimod cream or vehicle cream and applied study cream to five lesions on the scalp, forearm or upper trunk once daily, three days per week for up to 16 weeks. Each patient had punch biopsies of two distinct AK lesions: a lesion was biopsied before treatment to obtain baseline biomarker levels, and a different lesion was biopsied after 2 weeks of treatment. Biopsy specimens were examined using routine and immunohistochemical staining.
The imiquimod group showed statistically significant increases from baseline to week 2 in tissue biomarker levels for CD3, CD4, CD8, CD11c, CD86/CD11c, CD68, HLA-DR and TUNEL. No significant differences were seen for the vehicle group. Complete clearance of all treated AK lesions was achieved in five of 11 (45%) imiquimod patients and in none of six vehicle patients.
Imiquimod stimulates a cutaneous immune response characterized by increases in activated dendritic cells and CD4+ and CD8+ T cells.
5%咪喹莫特乳膏是一种局部应用的免疫反应调节剂，已被证明可有效治疗光化性角化病（AK）。咪喹莫特的治疗效果可能涉及激发针对异常细胞的皮肤免疫反应，这一假设基于完全清除率与局部皮肤反应（红斑、水肿、糜烂/溃疡、渗出/渗液和结痂/结壳）严重程度之间的强相关性；然而，尚无临床研究能确凿证明这一机制。
确定将咪喹莫特应用于AK皮损所诱导的细胞浸润性质，并研究参与皮肤免疫反应的细胞。
18名患者参与了这项I期随机、双盲、平行组、赋形剂对照研究。入选患者按2:1的比例随机分组，分别接受咪喹莫特乳膏或赋形剂乳膏，并将研究乳膏每日一次、每周三天涂抹于头皮、前臂或上躯干的5个皮损上，持续长达16周。每位患者对两个不同的AK皮损进行钻孔活检：一个皮损在治疗前活检以获取基线生物标志物水平，另一个不同的皮损在治疗2周后活检。活检标本采用常规和免疫组织化学染色进行检查。
咪喹莫特组从基线到第2周，CD3、CD4、CD8、CD11c、CD86/CD11c、CD68、HLA - DR和TUNEL的组织生物标志物水平在统计学上有显著升高。赋形剂组未见显著差异。11名接受咪喹莫特治疗的患者中有5名（45%）所有治疗的AK皮损完全清除，而6名接受赋形剂治疗的患者无一例完全清除。
咪喹莫特刺激皮肤免疫反应，其特征为活化树突状细胞以及CD4 +和CD8 + T细胞数量增加。
