Quantitative analyses of cytokine profiles reveal hormone-mediated modulation of cytokine profiles in recurrent spontaneous miscarriage.

Autor: Dingle K; Centre for Applied Mathematics and Bioinformatics, Department of Mathematics and Natural Sciences, Gulf University for Science and Technology, Hawally, Kuwait; Department of Computing and Mathematical Sciences, California Institute of Technology, Pasadena, CA, USA. Electronic address: dinglek@caltech.edu., Kassem OM; Centre for Applied Mathematics and Bioinformatics, Department of Mathematics and Natural Sciences, Gulf University for Science and Technology, Hawally, Kuwait., Azizieh F; Centre for Applied Mathematics and Bioinformatics, Department of Mathematics and Natural Sciences, Gulf University for Science and Technology, Hawally, Kuwait., AbdulHussain G; Department of Microbiology, Faculty of Medicine, Kuwait University, Kuwait., Raghupathy R; Department of Microbiology, Faculty of Medicine, Kuwait University, Kuwait.
Jazyk: angličtina
Zdroj: Cytokine [Cytokine] 2023 Apr; Vol. 164, pp. 156160. Date of Electronic Publication: 2023 Feb 18.
DOI: 10.1016/j.cyto.2023.156160
Abstrakt: Purpose: Cytokines play important roles in pregnancy complications. Some hormones such as estrogen, progesterone, 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 dydrogesterone on cytokine balances in women having recurrent spontaneous miscarriages.
Materials and Methods: Levels of eight cytokines (IFN-γ, IL-2, IL-6, IL-10, IL-13, IL-17, IL-23, TNF-α) 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-γ 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 contrasting groups identifies IFN-γ, IL-10 and IL-23 as especially noteworthy for both progesterone and dydrogesterone 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.
Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Kamaludin Dingle reports financial support was provided by Kuwait Foundation for the Advancement of Sciences.
(Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
Databáze: MEDLINE
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