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Changes in concentrations of cervicovaginal immune mediators across the menstrual cycle: a systematic review and meta-analysis of individual patient data

2022; BioMed Central; Volume: 20; Issue: 1 Linguagem: Inglês

10.1186/s12916-022-02532-9

1741-7015

Sean M. Hughes, Claire Levy, Ronit Katz, Erica M. Lokken, Melis N. Anahtar, Melissa Barousse Hall, Frideborg Bradley, Philip E. Castle, Valerie Cortez, Gustavo F. Doncel, Raina N. Fichorova, Paul L. Fidel, Keith R. Fowke, Suzanna C. Francis, Mimi Ghosh, Loris Y. Hwang, Mariel Jais, Vicky Jespers, Vineet Joag, Rupert Kaul, Jordan K. Kyongo, Timothy Lahey, Huiying Li, Julia Makinde, Lyle R. McKinnon, Anna‐Barbara Moscicki, Richard M. Novak, Mickey V. Patel, Intira Sriprasert, Andrea R. Thurman, Sergey Yegorov, Nelly Mugo, Alison C. Roxby, Elizabeth Micks, Florian Hladik, Salim S. Abdool Karim, Max Abou, Sharon M. Anderson, Aura Andreasen, Trong Ao, David F. Archer, Kevin K. Ariën, Kelly B. Arnold, Susana Asin, Susan Baden, Bernard Bagaya, Kathy Baisley, Emma Barnard, Angela Bartolf, Brian Bernick, Kenzie Birse, Andrea K. Boggild, Geneviève Boily-Larouche, Lucy A. Boksa, Brittany A. Bowman, Frederick P. Bowman, Kristina Broliden, Adam Burgener, Jozefien Buyze, Elizabeth H. Byrne, Neelima Chandra, Stacey Chapman, Hua Yun Chen, Juliana Cheruiyot, Ralph R. Chesson, Kathleen Cohen, Piet Cools, Catherine Cosgrove, Gary R. Coulton, Peggy A. Crowley‐Nowick, Tania Crucitti, Tina D. Cunningham, Susan Cu‐Uvin, Hassan Y. Dawood, Sinéad Delany‐Moretlwe, Krista L. Dong, Betty A. Donoval, Brenden Dufault, Kathleen Dunlap, Laura J. Dunphy, Robert P. Edwards, Lars Engstrand, Terri Espinosa, John V. Fahey, Titilayo Fashemi, J. Dennis Fortenberry, Jamie L. Freiermuth, Ronald M. Galiwango, Musie Ghebremichael, Sara V. Good, Odin Goovaerts, Parrie Graham, Liselotte Hardy, Klara Hasselrot, Richard Hayes, Betsy C. Herold, Carolina Herrera, Ronald C. Hershow, Allan Hildesheim, Sharon L. Hillier, Yanwen Hou, Hazel Huang, Sean M. Hughes, Loris Y. Hwang, Andrea Introini, Nasreen Ismail, Terry A. Jacot, Mariel Jais, Vicky Jespers, Vineet Joag, Christine Johnston, C. K. Jones, Sarah Joseph, Saidi Kapiga, John C. Kappes, Joshua Kimani, Makobu Kimani, Thomas Kimble, Noah Kiwanuka, Monika M. Kowatsch, Jessie Kwatampora, Douglas S. Kwon, Julie Lajoie, Alan Landay, Douglas A. Lauffenburger, Dara A. Lehman, Alasdair Leslie, Lenine J. P. Liebenberg, Phil Lieberman, Vitali Lounev, Yifei Ma, Amanda Mabhula, Jennifer Mabuka, Kaballa Maganja, Jeanne Marrazzo, Lindi Masson, Kenneth H. Mayer, Stuart McCorrister, Joris Menten, Pedro M. M. Mesquita, Johan Míchiels, Sebastián Mirkin, Amber Moodley, Juliet Mpendo, Lucy R. Mukura, Mary Mwaura, Gilles Ndayisaba, Thumbi Ndung’u, Jane Njoki, Laura Noël‐Romas, Billy Nyanga, Christina Ochsenbauer, Katherine Odem‐Davis, Gregory S. Olson, Kenneth Omollo, Donald P. Orr, Julie Overbaugh, Julius Oyugi, Nikita Padavattan, Tarita Pakrashi, Urvashi Pandey, Jo‐Ann S. Passmore, Terri Pustilnik, Lorna K. Rabe, Nicola Richardson‐Harman, Christiane Rollenhagen, Laura Romas, Richard M. Rossoll, Jill L. Schwartz, Mark E. Scott, Maike Seifert, A. Shah, Kamnoosh Shahabi, Robin J. Shattock, Zheng Shen, Baochen Shi, Sengeziwe Sibeko, Yan Song, Gregory T. Spear, Brian S. Starkman, Howard D. Strickler, Jan L. Sumerel, Egbert Tannich, Katherine P. Theall, Annelie Tjernlund, Janneke van de Wijgert, Barbara Van Der Pol, Guido Vanham, Bruce D. Walker, Joan L. Walker, Deborah Watson‐Jones, Hugo Wefer, Garrett Westmacott, Charles R. Wira, Peter F. Wright, Naji Younes, Nazita Yousefieh,

Reproductive Physiology in Livestock

Abstract Background 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. Methods 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. Results 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. Conclusions 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.