Guiding the vaginal microbicide trials with biomarkers of inflammation
Guiding the vaginal microbicide trials with biomarkers of inflammation
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DOI：
10.1097/00126334-200410013-00010
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发表时间：
2004-10-01
影响因子：
3.6
通讯作者：
Fichorova, RN
中科院分区：
文献类型：
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作者：
Fichorova, RN
本文讨论了细胞因子模式作为阴道炎症的潜在生物标志物，这是需要的局部杀微生物剂产品的安全性评价，以预防性传播的HIV-1感染。为了有效，阴道抗HIV-1杀微生物剂应避免促进经上皮病毒渗透和复制的促炎反应。促炎细胞因子和抗炎细胞因子在HIV-1的发病、传播、易感性和耐药性中发挥双向作用。先前的研究已经表明，许多这些粘膜屏障功能的关键介质（例如IL-1、IL-1受体拮抗剂、IL-6、TNF-α、TNF-受体II、转化生长因子β、IL-10、IL-12、IL-8、巨噬细胞抑制蛋白1等）在胃粘膜中的表达与胃粘膜屏障功能密切相关。可以使用非侵入性采样技术在健康或受感染个体的阴道分泌物中检测到。作为两项杀微生物剂试验的一部分，我们测量了在产品使用前和产品使用后第7天和第14天获得的291个宫颈阴道灌洗液样本中的IL-1 α、IL-1 β、IL-1受体拮抗剂、TNF-α和IL-8。我们发现阴道液中的阴道制剂、温度和基质特异性因素可能会干扰细胞因子检测，因此必须对各种采集程序和细胞因子测定的特定方案进行验证。我们的研究结果表明，细胞因子动力学的组合模式，而不是单独的测量可能区分杀微生物剂安全性试验中的促炎产品相关的影响。需要更多的研究来建立细胞因子粘膜基线和遗传因素，性交，月经周期，运动，激素，压力和感染的调节，然后才能建立临床试验入组标准，预测副作用/不良事件和最终杀微生物剂的益处。
This article discusses cytokine patterns as potential biomarkers of vaginal inflammation, which are needed for the safety evaluation of topical microbicide products for the prevention of sexually transmitted HIV-1 infection. In order to be effective, the vaginal anti-HIV-1 microbicides should avoid proinflammatory responses that facilitate transepithelial viral penetration and replication. Pro-inflammatory and anti-inflammatory cytokines play bi-directional roles in HIV-1 pathogenesis, transmission, susceptibility and resistance. Previous research has shown that many of these key mediators of mucosal barrier function (e.g. IL-1, IL-1 receptor antagonist, IL-6, TNF-alpha, TNF-receptor II, transforming growth factor beta, IL-10, IL-12, IL-8, macropbage inhibitory protein 1, etc.) can be detected in the vaginal secretions of healthy or infected individuals using non-invasive sampling techniques. As part of two microbicide trials, we measured IL-1alpha, IL-1beta, IL-1 receptor antagonist, TNF-alpha and IL-8 in 291 cervicovaginal lavage samples obtained before product use and at the seventh and 14th day after product use. We showed that vaginal formulations, temperature and matrix-specific factors in the vaginal fluids may interfere with cytokine detection, and therefore specific protocols must be validated for various collection procedures and cytokine assays. Our results suggest that combined patterns of cytokine dynamics rather than individual measurements might distinguish proinflammatory product-related effects in microbicide safety trials. More research is needed to establish cytokine mucosal baselines and modulation by genetic factors, sexual intercourse, menstrual cycle, exercise, hormones, stress and infections before guidelines can be established for clinical trial enrollment criteria, the prediction of side/adverse events and ultimately microbicide benefit prognostication.