Imiquimod-induced regression of actinic keratosis is associated with infiltration by T lymphocytes and dendritic cells: a randomized controlled trial
Imiquimod-induced regression of actinic keratosis is associated with infiltration by T lymphocytes and dendritic cells: a randomized controlled trial
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DOI：
10.1111/j.1365-2133.2005.06932.x
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发表时间：
2006-01-01
影响因子：
10.3
通讯作者：
Halliday, GM
中科院分区：
文献类型：
--
作者：
Ooi, T;Barnetson, RS;Halliday, GM
5%咪喹莫特乳膏是一种局部应用的免疫反应调节剂，已被证明能有效治疗光化性角化病（AK）。咪喹莫特的治疗作用可能涉及激发针对异常细胞的皮肤免疫应答，这是基于完全清除率与局部皮肤反应严重程度之间的强相关性的假设（红斑、水肿、糜烂/溃疡、渗出/渗出和结痂/结痂）;但是，在此情况下，目的确定应用咪喹莫特治疗AK损伤诱导的细胞浸润的性质，方法18例患者参加了这项I期、随机、双盲、平行组、载体对照研究。入组的患者以2：1的比例随机接受咪喹莫特乳膏或媒介物乳膏，并将研究乳膏应用于头皮、前臂或上躯干上的五个病灶，每天一次，每周三天，持续长达16周。每例患者均对两个不同的AK病变进行穿刺活检：治疗前对一个病变进行活检以获得基线生物标志物水平，治疗2周后对另一个病变进行活检。结果治疗2周后，咪喹莫特组患者外周血中CD 3、CD 4、CD 8、CD 11 c、CD 86/CD 11 c、CD 68、HLA-DR和TUNEL等组织生物标志物水平较治疗前明显升高，差异有统计学意义（P <0.05）。溶媒组未观察到显著差异。所有治疗的AK病灶完全清除，实现了11（45%）咪喹莫特患者中的5个，没有6个车辆patients.Conclusions咪喹莫特刺激皮肤免疫反应的特点是增加活化的树突状细胞和CD 4+和CD 8 + T细胞。
Background 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.Objectives 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.Methods 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.Results 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.Conclusions Imiquimod stimulates a cutaneous immune response characterized by increases in activated dendritic cells and CD4+ and CD8+ T cells.