Department of Obstetrics and Gynaecology, Erasmus University Medical Center, Rotterdam, The Netherlands.
Int J Cancer. 2011 May 15;128(10):2463-9. doi: 10.1002/ijc.25573.
Imiquimod has been shown to be an effective treatment for usual type vulvar intraepithelial neoplasia (uVIN). Since local inflammation and burning are common side effects, patients often use nonsteroidal anti-inflammatory drugs (NSAIDs). Our study investigated whether NSAID-use, which has been documented to inhibit the cell-mediated immune response, interferes with the outcome of imiquimod treatment. Monocyte-derived dendritic cells (moDCs) and Langerhans cells (moLCs) were cultured in the presence of NSAIDs. The expression of relevant surface markers (CD80, CD86, CD40, HLA-DR, CCR6 and CCR7), stimulatory function, and cytokine production were evaluated. Furthermore, we analyzed in uVIN patients whether frequent NSAID-use had an effect on the clinical response and on immunocompetent cell counts before and after imiquimod treatment. Although an effect was observed on the expression of moDC and moLC maturation markers, NSAIDs did not affect the ability of moDCs and moLCs to stimulate allogeneic T-cell proliferation, or the production of cytokines in an allogeneic T-cell stimulation assay. In agreement with this, in uVIN patients treated with imiquimod, no interference of frequent NSAID-use with clinical outcome was observed. However, we did notice that high CD1a(+) and CD207(+) cell counts in frequent NSAID-users before treatment seemed to predict a favourable response to imiquimod treatment. Our data indicate that NSAID-use does not seem to interfere with moDC and moLC function and does not interfere with immunomodulatory properties of imiquimod in uVIN patients. Therefore, NSAIDs can safely be used to reduce imiquimod side effects in uVIN patients during treatment.
咪喹莫特已被证明是治疗普通型外阴上皮内瘤变(uVIN)的有效方法。由于局部炎症和烧灼感是常见的副作用,患者通常会使用非甾体抗炎药(NSAIDs)。我们的研究调查了 NSAIDs 的使用是否会干扰咪喹莫特治疗的结果,因为 NSAIDs 已被证明会抑制细胞介导的免疫反应。我们在 NSAIDs 存在的情况下培养单核细胞衍生的树突状细胞(moDCs)和朗格汉斯细胞(moLCs)。评估了相关表面标志物(CD80、CD86、CD40、HLA-DR、CCR6 和 CCR7)的表达、刺激功能和细胞因子产生。此外,我们还分析了 uVIN 患者中频繁使用 NSAIDs 是否会对临床反应以及咪喹莫特治疗前后免疫活性细胞计数产生影响。尽管观察到 moDC 和 moLC 成熟标志物的表达受到影响,但 NSAIDs 并未影响 moDCs 和 moLCs 刺激同种异体 T 细胞增殖的能力,也未影响同种异体 T 细胞刺激试验中细胞因子的产生。与此一致的是,在接受咪喹莫特治疗的 uVIN 患者中,未观察到频繁使用 NSAIDs 会干扰临床结局。然而,我们确实注意到,在治疗前频繁使用 NSAIDs 的患者中,高 CD1a(+)和 CD207(+)细胞计数似乎预示着对咪喹莫特治疗有良好的反应。我们的数据表明,NSAIDs 的使用似乎不会干扰 moDC 和 moLC 的功能,也不会干扰 uVIN 患者咪喹莫特的免疫调节特性。因此,在 uVIN 患者接受咪喹莫特治疗期间,为了减轻其副作用,可以安全地使用 NSAIDs。