PRO 2000 elicits a decline in genital tract immune mediators without compromising intrinsic antimicrobial activity
PRO 2000 elicits a decline in genital tract immune mediators without compromising intrinsic antimicrobial activity
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DOI：
10.1097/qad.0b013e328013d9b5
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发表时间：
2007-02-01
期刊：
影响因子：
3.8
通讯作者：
Herold, Betsy C.
中科院分区：
文献类型：
--
作者：
Keller, Marla J.;Guzman, Esmeralda;Herold, Betsy C.
目的：阴道杀微生物剂应在不破坏粘膜环境或其宿主防御介质的情况下防止感染。本研究的目的是检查14个每天应用的0.5% PRO 2000或安慰剂凝胶介质的粘膜免疫和内在antimicrobial activity.Design和方法的效果：一个随机的，前瞻性的，双盲，安慰剂对照研究进行了24个健康，禁欲的妇女。在研究第0、7、14和21天收集的宫颈阴道灌洗液样品中测定细胞因子、趋化因子、防御素和其他保护因子的水平以及内在抗菌活性。相反，与安慰剂组相比，药物组的细胞因子和保护因子，包括白细胞介素（IL）-1受体拮抗剂，免疫球蛋白和人β-防御素2均较低。所有介质在第21天恢复至基线。与口服避孕药的女性相比，骑自行车的女性在研究第7天和/或第14天的大多数蛋白质水平较低;然而，与安慰剂凝胶相比，接受PRO 2000的女性下降幅度更大。保护因素的减少与内在抗病毒（HIV或单纯疱疹病毒）活性或抗菌活性（大肠杆菌或金黄色葡萄球菌）的损失无关。结论：与壬苯醇醚-9的经验相反，PRO 2000没有引发宫颈阴道分泌物的炎症反应。粘膜免疫介质略有减少，但这种损失与内在抗菌活性的降低无关。(c)2007年利平科特威廉姆斯&威尔金斯。
Objective: Vaginal microbicides should protect against infection without disrupting the mucosal environment or its mediators of host defense. The objective of this study was to examine the effect of 14 daily applications of 0.5% PRO 2000 or placebo gel on mediators of mucosal immunity and intrinsic antimicrobial activity.Design and methods: A randomized, prospective, double-blind, placebo-controlled study was conducted among 24 healthy, abstinent women. Levels of cytokines, chemokines, defensins, and other protective factors and intrinsic antimicrobial activity were determined in cervicovaginal lavage samples collected on study days 0, 7, 14, and 21.Results: No increase in pro-inflammatory cytokines was observed. Rather cytokines and protective factors including interleukin (IL)-1 receptor antagonist, immunoglobulins and human beta-defensin 2 were lower in the drug compared with the placebo group. All of the mediators returned towards baseline on day 21. Women who were cycling had lower levels of most proteins on study days 7 and/or 14 compared with women on oral contraceptives; however, the magnitude of decline was greater in women who received PRO 2000 compared with placebo gel. The reduction in protective factors was not associated with a loss in the intrinsic anti-viral (HIV or herpes simplex virus) activity or anti-bacterial activity (Escherichia coli or Staphylococcus aureus).Conclusion: In contrast to experience with nonoxynol-9, PRO 2000 did not trigger an inflammatory response in cervicovaginal secretions. There was a modest reduction in mucosal immune mediators, but this loss was not associated with a reduction in intrinsic antimicrobial activity. (c) 2007 Lippincott Williams & Wilkins.