Enhancement of the innate and cellular immune response in patients with genital warts treated with topical imiquimod cream 5%
Enhancement of the innate and cellular immune response in patients with genital warts treated with topical imiquimod cream 5%
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DOI：
10.1016/s0166-3542(99)00033-9
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发表时间：
1999-08-01
影响因子：
7.6
通讯作者：
Slade, HB
中科院分区：
文献类型：
--
作者：
Arany, I;Tyring, SK;Slade, HB
在一项双盲、安慰剂对照研究中评估了5%咪喹莫特乳膏局部应用于生殖器疣患者的作用机制。咪喹莫特（16名患者）或安慰剂（3名患者）每周应用三次，持续长达16周。所有接受咪喹莫特治疗的患者的总疣面积减少大于或等于75%，而只有三分之一的安慰剂治疗患者有类似的减少。在研究前、第6周和治疗结束时进行疣活检。人乳头瘤病毒（HPV）DNA的聚合酶链反应（PCR）和信使（m）RNA的逆转录酶（RT）-PCR用于识别这些活检中的细胞因子、细胞标志物、病毒基因产物和细胞周期标志物。用免疫应答调节剂咪喹莫特治疗，刺激干扰素（IFN）-α、IFN-γ和2 '，5'寡腺苷酸合成酶（2 '，5'-AS）的mRNA显著增加，以及肿瘤坏死因子（TNF）-α和白细胞介素-12 p40增加的趋势。在咪喹莫特治疗的患者中也观察到CD 4 mRNA的显著增加和CD 8增加的趋势，表明细胞介导的免疫应答的激活。咪喹莫特给药还与通过HPV DNA和L1 mRNA测量的病毒载量的显著降低相关。对HPV标志物的影响伴随着细胞增殖标志物的mRNA表达的明显降低和角质形成细胞分化标志物和肿瘤抑制因子的mRNA表达的增加。(C)1999 Elsevier Science B. V.保留所有权利。
The mechanism of action of imiquimod 5% cream applied topically to patients with genital warts was evaluated in a double-blind, placebo-controlled study. Imiquimod (16 patients) or placebo (three patients) was applied three times per week for up to 16 weeks. All imiquimod-treated patients had a greater than or equal to 75% reduction in total wart area while only one of three placebo-treated patients had a similar reduction. Wart biopsies were taken at prestudy, week 6, and end of treatment. Polymerase chain reaction (PCR) for human papillomavirus (HPV) DNA and reverse transcriptase (RT)-PCR for messenger (m)RNAs were used to identify cytokines, cellular markers, viral gene products, and cell cycle markers in these biopsies. Treatment with imiquimod, an immune response modifier, stimulated significant increases in mRNA for interferon (IFN)-alpha, IFN-gamma and 2',5' oligoadenylate synthetase (2',5'-AS) as well as a tendency towards increases in tumor necrosis factor (TNF)-alpha and interleukin-12 p40. Significant increases in mRNA for CD4 and a trend toward increases in CD8 were also observed in imiquimod-treated patients, suggesting activation of a cell mediated immune response. Imiquimod administration was also associated with a significant decrease in viral load as measured by HPV DNA and L1 mRNA, The effects on HPV markers were accompanied by an apparent decrease in mRNA expression for markers of cell proliferation and an increase in mRNA for markers of keratinocyte differentiation and tumor suppressors. (C) 1999 Elsevier Science B.V. All rights reserved.