期刊
CYTOKINE
卷 164, 期 -, 页码 -出版社
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.cyto.2023.156160
关键词
Cytokines; Miscarriage; Multivariate methods; Effect size; Cytokine importances; Immune System
This study examined the effects of estrogen, progesterone, and dydrogesterone on cytokine profiles in women with recurrent spontaneous miscarriages. The results showed that estrogen had the fewest effects on cytokines, while progesterone and dydrogesterone affected seven out of eight cytokines. The new statistical method identified IFN-gamma, IL-10, and IL-23 as particularly significant for progesterone and dydrogesterone treatments.
Purpose: Cytokines play important roles in pregnancy complications. Some hormones such as estrogen, proges-terone, and dydrogesterone have been shown to alter cytokine profiles. Understanding how cytokine profiles are affected by these hormones is therefore an important step towards immunomodulatory therapies for pregnancy complications. We analyse previously published data on the effects of estrogen, progesterone, and dydroges-terone on cytokine balances in women having recurrent spontaneous miscarriages.Materials and methods: Levels of eight cytokines (IFN-gamma, IL-2, IL-6, IL-10, IL-13, IL-17, IL-23, TNF-alpha) from n = 22 women presenting unexplained recurrent spontaneous miscarriages were studied. Cytokine values were recorded after in vitro exposure of peripheral blood cells to estrogen, progesterone, and dydrogesterone. We expand on earlier analysis of the dataset by employing different statistical techniques including effect sizes for individual cytokine values, a more powerful statistical test, and adjusting p-values for multiple comparisons. We employ multivariate analysis methods, including to determine the relative magnitude of the effects of the hormone therapies on cytokines. A new statistical method is introduced based on pairwise distances able to accommodate complex relations in cytokine profiles.Results: We report several statistically significant differences in individual cytokine values between the control group and each hormone treated group, with estrogen affecting the fewest cytokines, and progesterone and dydrogesterone both affecting seven out of eight cytokines. Exposure to estrogen produces no large effects sizes however, while IFN-gamma and IL-17 show large effect sizes for both progesterone and dydrogesterone, among other cytokines. Our new method for identifying which collections (i.e. subsets) of cytokines best distinguish con-trasting groups identifies IFN-gamma, IL-10 and IL-23 as especially noteworthy for both progesterone and dydroges-terone treatments.Conclusions: While some statistically significant differences in cytokine levels after exposure to estrogen are found, these have small effect sizes and are unlikely to be clinically relevant. Progesterone and dydrogesterone both induce statistically significant and large effect-size differences in cytokine levels, hence therapy with these two progestogens is more likely to be clinically relevant. Univariate and multivariate methods for identifying cytokine importances provide insight into which groups of cytokines are most affected and in what ways by therapies.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据