背景:月经周期中的激素变化在形成宫颈阴道道的免疫力中起着关键作用。宫颈阴道液含有细胞因子,趋化因子,免疫球蛋白,和其他免疫介质。许多研究表明,这些免疫介质的浓度在整个月经周期中都会发生变化,但是这些研究经常显示出不一致的结果。我们对月经周期的免疫学相关性的理解仍然有限,可以通过对现有证据的荟萃分析来改善。
方法:我们使用个体参与者数据对整个月经周期的宫颈阴道免疫介质浓度进行了系统评价和荟萃分析。研究资格包括对周期阶段的严格定义(通过孕酮或自上次月经期以来的天数),并且不使用激素避孕或宫内节育器。我们使用逆方差合并进行了随机效应荟萃分析,以估计卵泡期和黄体期之间的浓度差异。此外,我们进行了一项新的实验室研究,测量宫颈阴道灌洗样品中的选择免疫介质。
结果:我们筛选了1570篇摘要,确定了71篇符合条件的研究。我们分析了31项研究的数据,包括对871名参与者的2112个样本进行的77个免疫介质的39,589个浓度测量。对53种免疫介质进行Meta分析。抗体,CC型趋化因子,MMPs,IL-6,IL-16,IL-1RA,G-CSF,GNLY,和ICAM1在黄体期低于卵泡期。只有IL-1α,HBD-2和HBD-3在黄体期升高。CXCL8、9和10干扰素的相位之间变化最小,TNF,SLPI,埃拉芬,溶菌酶,乳铁蛋白,和白细胞介素1β,2、10、12、13和17A。此处列出的所有免疫介质的证据等级强度为中等至高。
结论:尽管宫颈阴道免疫介质测量的可变性,我们的荟萃分析显示月经周期期间有明显且一致的变化.许多免疫介质在黄体期较低,包括趋化因子,抗体,基质金属蛋白酶,和几种白介素.只有白细胞介素-1α和β-防御素在黄体期更高。这些周期性差异可能会对免疫力产生影响,易感染,和生育能力。我们的研究强调在未来的研究中需要控制月经周期对免疫介质的影响。
Hormonal changes during the menstrual cycle play a key role in shaping immunity in the cervicovaginal tract. Cervicovaginal fluid contains cytokines, chemokines, immunoglobulins, and other immune mediators. Many studies have shown that the concentrations of these immune mediators change throughout the menstrual cycle, but the studies have often shown inconsistent results. Our understanding of immunological correlates of the menstrual cycle remains limited and could be improved by meta-analysis of the available evidence.
We performed a systematic
review and meta-analysis of cervicovaginal immune mediator concentrations throughout the menstrual cycle using individual participant data. Study eligibility included strict definitions of the cycle phase (by progesterone or days since the last menstrual period) and no use of hormonal contraception or intrauterine devices. We performed random-effects meta-analyses using inverse-variance pooling to estimate concentration differences between the follicular and luteal phases. In addition, we performed a new laboratory study, measuring select immune mediators in cervicovaginal lavage samples.
We screened 1570 abstracts and identified 71 eligible studies. We analyzed data from 31 studies, encompassing 39,589 concentration measurements of 77 immune mediators made on 2112 samples from 871 participants. Meta-analyses were performed on 53 immune mediators. Antibodies, CC-type chemokines, MMPs, IL-6, IL-16, IL-1RA, G-CSF, GNLY, and ICAM1 were lower in the luteal phase than the follicular phase. Only IL-1α, HBD-2, and HBD-3 were elevated in the luteal phase. There was minimal change between the phases for CXCL8, 9, and 10, interferons, TNF, SLPI, elafin, lysozyme, lactoferrin, and interleukins 1β, 2, 10, 12, 13, and 17A. The GRADE strength of evidence was moderate to high for all immune mediators listed here.
Despite the variability of cervicovaginal immune mediator measurements, our meta-analyses show clear and consistent changes during the menstrual cycle. Many immune mediators were lower in the luteal phase, including chemokines, antibodies, matrix metalloproteinases, and several interleukins. Only interleukin-1α and beta-defensins were higher in the luteal phase. These cyclical differences may have consequences for immunity, susceptibility to infection, and fertility. Our study emphasizes the need to control for the effect of the menstrual cycle on immune mediators in future studies.