FREE SHIPPING over $40
OVER 9000 FIVE-STAR REVIEWS
5% OFF ALL SUBSCRIPTIONS
100% HAPPINESS GUARANTEE
Analyze Diet
0
Home / Equine Research Bank / Am J Reprod Immunol / Interleukin-6 pathobiology in equine placental infection.
American journal of reproductive immunology (New York, N.Y. : 1989)2021; 85(5); e13363; doi: 10.1111/aji.13363

Interleukin-6 pathobiology in equine placental infection.

Abstract: Ascending placentitis is the leading cause of abortion in the horse. Interleukin (IL)-6 is considered predictive of placental infection in other species, but little is understood regarding its role in the pathophysiology of ascending placentitis. Sub-acute ascending placentitis was induced via trans-cervical inoculation of S zooepidemicus, and various fluids/serum/tissues collected 8 days later. Concentrations of IL-6 were detected within fetal fluids and serum in inoculated (n = 6) and control (n = 6) mares. RNASeq was performed on the placenta (endometrium and chorioallantois) to assess transcripts relating to IL-6 pathways. IHC was performed for immunolocalization of IL-6 receptor (IL-6R) in the placenta. IL-6 concentrations increased in allantoic fluid following inoculation, with a trend toward an increase in amniotic fluid. Maternal serum IL-6 was increased in inoculated animals, while no changes were noted in fetal serum. mRNA expression of IL-6-related transcripts within the chorioallantois indicates that IL-6 is activating the classical JAK/STAT pathway, thereby acting as anti-inflammatory, anti-apoptotic, and pro-survival. The IL-6R was expressed within the chorioallantois, indicating a paracrine signaling pathway of maternal IL-6 to fetal IL-6R. IL-6 plays a crucial role in the placental response to induction of sub-acute equine ascending placentitis, and this could be noted in amniotic fluid, allantoic fluid, and maternal serum. Additionally, IL-6 is acting as anti-inflammatory in this disease, potentially altering disease progression, impeding abortion signals, and assisting with the production of a viable neonate.
© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Get Full Text
Publication Date: 2021-02-09 PubMed ID: 33098605DOI: 10.1111/aji.13363Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
LinkedInCopy
  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The study investigates the role of Interleukin-6 (IL-6) in ascending placentitis, a leading cause of abortion in horses, showing that the increase of this protein could contribute to the anti-inflammatory response in the disease, potentially altering progression, preventing abortion, and supporting the production of viable offspring.

Introduction

  • The paper focuses on the function of Interleukin-6 (IL-6) — a protein involved in infection response — in sub-acute ascending placentitis in mares. Ascending placentitis is a common cause of fetal loss in horses but the involvement of IL-6 in this disease is not adequately explored.

Methodology

  • Sub-acute ascending placentitis was triggered in the subjects by inoculating them with Streptococcus zooepidemicus, a bacterium often associated with the disease.
  • Eight days later, various fluids, serum and tissues were collected from both the infected horses (6 in number) and the control group.
  • Concentrations of IL-6 were determined in the collected samples.
  • RNA Sequencing was executed on the placenta (endometrium and chorioallantois) to explore transcripts related to IL-6 pathways.
  • Immunohistochemistry (IHC) was used to identify the location of the IL-6 receptor (IL-6R) in the placenta.

Findings

  • Post inoculation, levels of IL-6 increased in allantoic fluid, with a similar increase trend noted in amniotic fluid.
  • In the serum of the inoculated mares, IL-6 levels were found to be higher than in the control group. In contrast, no changes in IL-6 concentration were observed in the serum of fetuses.
  • The study detected an upregulation in mRNA expression of IL-6-related transcripts within the chorioallantois, indicating that IL-6 could be activating the classical JAK/STAT pathway.
  • IL-6R was identified within the chorioallantois, suggesting that maternal IL-6 could influence fetal IL-6R through a paracrine signalling pathway.

Conclusion

  • IL-6 has a vital role in the placental response to the induction of sub-acute equine ascending placentitis, evident in amniotic fluid, allantoic fluid, and maternal serum.
  • It further proposes that IL-6 may function as an anti-inflammatory agent in this disease, potentially altering disease progression, blocking signals leading to abortion, and facilitating the production of a viable neonate.

Cite This Article

APA
Fedorka CE, Scoggin KE, El-Sheikh Ali H, Loux SC, Dini P, Troedsson MHT, Ball BA. (2021). Interleukin-6 pathobiology in equine placental infection. Am J Reprod Immunol, 85(5), e13363. https://doi.org/10.1111/aji.13363

Publication

American journal of reproductive immunology (New York, N.Y. : 1989)
ISSN: 1600-0897
NlmUniqueID: 8912860
Country: Denmark
Language: English
Volume: 85
Issue: 5
Pages: e13363

Researcher Affiliations

Fedorka, Carleigh E
  • Department of Veterinary Science, University of Kentucky, Lexington, KY, USA.
Scoggin, Kirsten E
  • Department of Veterinary Science, University of Kentucky, Lexington, KY, USA.
El-Sheikh Ali, Hossam
  • Department of Veterinary Science, University of Kentucky, Lexington, KY, USA.
  • Department of Theriogenology, University of Mansoura, Dakahlia, Egypt.
Loux, Shavahn C
  • Department of Veterinary Science, University of Kentucky, Lexington, KY, USA.
Dini, Pouya
  • Department of Veterinary Science, University of Kentucky, Lexington, KY, USA.
  • Department of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
Troedsson, Mats H T
  • Department of Veterinary Science, University of Kentucky, Lexington, KY, USA.
Ball, Barry A
  • Department of Veterinary Science, University of Kentucky, Lexington, KY, USA.

MeSH Terms

  • Amniotic Fluid / immunology
  • Animals
  • Endometrium / immunology
  • Female
  • Horse Diseases / blood
  • Horse Diseases / genetics
  • Horse Diseases / immunology
  • Horses
  • Interleukin-6 / blood
  • Interleukin-6 / genetics
  • Interleukin-6 / immunology
  • Placenta / immunology
  • Placenta Diseases / blood
  • Placenta Diseases / genetics
  • Placenta Diseases / immunology
  • Placenta Diseases / veterinary
  • Pregnancy
  • Receptors, Interleukin-6 / genetics
  • Receptors, Interleukin-6 / immunology
  • Streptococcal Infections / blood
  • Streptococcal Infections / genetics
  • Streptococcal Infections / immunology
  • Streptococcal Infections / veterinary
  • Streptococcus equi

References

This article includes 88 references
  1. Hong CB, Donahue JM, Giles RC. Equine abortion and stillbirth in central Kentucky during 1988 and 1989 foaling seasons.. J Vet Diagn Invest 1993;5(4):560-566.
  2. Renaudin CD, Troedsson MHT, Gillis CL. Ultrasonographic evaluation of the equine placenta by transrectal and transabdominal approach in the normal pregnant mare.. Theriogenology 1997;47(2):559-573.
  3. Canisso IF, Ball BA, Cray C. Serum amyloid A and haptoglobin concentrations are increased in plasma of mares with ascending placentitis in the absence of changes in peripheral leukocyte counts or fibrinogen concentration.. Am J Reprod Immunol 2014;72(4):376-385.
  4. Canisso IF, Ball BA, Scoggin KE, Squires EL, Williams NM, Troedsson MH. Alpha-fetoprotein is present in the fetal fluids and is increased in plasma of mares with experimentally induced ascending placentitis.. Anim Reprod Sci 2015;154:48-55.
  5. LeBlanc MM, Giguere S, Brauer K. Premature delivery in ascending placentitis is associated with increased expression of placental cytokines and allantoic fluid prostaglandins E2 and F2alpha.. Theriogenology 2002;58:841-844.
  6. Morris S, Kelleman AA, Stawicki RJ. Transrectal ultrasonography and plasma progestin profiles identifies feto-placental compromise in mares with experimentally induced placentitis.. Theriogenology 2007;67(4):681-691.
  7. Canisso IF, Ball BA, Esteller-Vico A, Williams NM, Squires EL, Troedsson MH. Changes in maternal androgens and oestrogens in mares with experimentally-induced ascending placentitis.. Equine Vet J 2017;49(2):244-249.
  8. Wynn MAA, Ball BA, May J. Changes in maternal pregnane concentrations in mares with experimentally-induced, ascending placentitis.. Theriogenology 2018;122:130-136.
  9. El-Sheikh Ali H, Legacki EL, Scoggin KE. Steroid synthesis and metabolism in the equine placenta during placentitis.. Reproduction 2020;159(3):289-302.
  10. Kemp MW. Preterm birth, intrauterine infection, and fetal inflammation.. Front Immunol 2014;5:574.
  11. Keelan JA. Intrauterine inflammatory activation, functional progesterone withdrawal, and the timing of term and preterm birth.. J Reprod Immunol 2018;125:89-99.
  12. Cobo T, Kacerovsky M, Holst RM. Intra-amniotic inflammation predicts microbial invasion of the amniotic cavity but not spontaneous preterm delivery in preterm prelabor membrane rupture.. Acta Obstet Gynecol Scand 2012;91(8):930-935.
  13. Cobo T, Kacerovsky M, Palacio M. Intra-amniotic inflammatory response in subgroups of women with preterm prelabor rupture of the membranes.. PLoS One 2012;7(8):e43677.
  14. Cobo T, Kacerovsky M, Palacio M. A prediction model of histological chorioamnionitis and funisitis in preterm prelabor rupture of membranes: analyses of multiple proteins in the amniotic fluid.. J Matern Fetal Neonatal Med 2012;25(10):1995-2001.
  15. Holst RM, Hagberg H, Wennerholm UB. Prediction of spontaneous preterm delivery in women with preterm labor: analysis of multiple proteins in amniotic and cervical fluids.. Obstet Gynecol 2009;114(2 Pt 1):268-277.
  16. Fedorka CE, Barry AB, Scoggin KE. The feto-maternal immune response to equine placentitis.. Am J Reprod Immunol 2019;82:e13179.
  17. LeBlanc MM, Giguère S, Lester GD, Brauer K, Paccamonti DL. Relationship between infection, inflammation and premature parturition in mares with experimentally induced placentitis.. Equine Vet J Suppl 2012;41:8-14.
  18. Fernandes CB, Ball BA, Loux SC. Uterine cervix as a fundamental part of the pathogenesis of pregnancy loss associated with ascending placentitis in mares.. Theriogenology 2020;145:167-175.
  19. Cobo T, Tsiartas P, Kacerovsky M. Maternal inflammatory response to microbial invasion of the amniotic cavity: analyses of multiple proteins in the maternal serum.. Acta Obstet Gynecol Scand 2013;92(1):61-68.
  20. Holst RM, Hagberg H, Wennerholm U-B, Skogstrand K, Thorsen P, Jacobsson B. Prediction of microbial invasion of the amniotic cavity in women with preterm labour: analysis of multiple proteins in amniotic and cervical fluids.. BJOG 2011;118(2):240-249.
  21. Dudley DJ, Hunter C, Mitchell MD, Varner MW. Clinical value of amniotic fluid interleukin-6 determinations in the management of preterm labour.. Br J Obstet Gynaecol 1994;101(7):592-597.
  22. Kacerovsky M, Musilova I, Jacobsson B. Vaginal fluid IL-6 and IL-8 levels in pregnancies complicated by preterm prelabor membrane ruptures.. J Matern Fetal Neonatal Med 2015;28(4):392-398.
  23. Musilova I, Bestvina T, Hudeckova M. Vaginal fluid interleukin-6 concentrations as a point-of-care test is of value in women with preterm prelabor rupture of membranes.. Am J Obstet Gynecol 2016;215(5):619 e1-619 e12.
  24. Kacerovsky M, Musilova I, Jacobsson B. Cervical fluid IL-6 and IL-8 levels in pregnancies complicated by preterm prelabor rupture of membranes.. J Matern Fetal Neonatal Med 2015;28(2):134-140.
  25. Kacerovsky M, Musilova I, Jacobsson B. Cervical and vaginal fluid soluble Toll-like receptor 2 in pregnancies complicated by preterm prelabor rupture of membranes.. J Matern Fetal Neonatal Med 2015;28(10):1116-1122.
  26. Kacerovsky M, Musilova I, Bestvina T, Stepan M, Cobo T, Jacobsson B. Preterm prelabor rupture of membranes between 34 and 37 Weeks: a point-of-care test of vaginal fluid interleukin-6 concentrations for a noninvasive detection of intra-amniotic inflammation.. Fetal Diagn Ther 2018;43(3):175-183.
    doi: 10.1159/000477617google scholar: lookup
  27. Park JW, Park KH, Kook SY, Jung YM, Kim YM. Immune biomarkers in maternal plasma to identify histologic chorioamnionitis in women with preterm labor.. Arch Gynecol Obstet 2019;299(3):725-732.
  28. Martinez-Portilla RJ, Hawkins-Villarreal A, Alvarez-Ponce P. Maternal serum interleukin-6: a non-invasive predictor of histological chorioamnionitis in women with preterm-prelabor rupture of membranes.. Fetal Diagn Ther 2019;45(3):168-175.
  29. Duncombe G, Veldhuizen RAW, Gratton RJ, Han VKM, Richardson BS. IL-6 and TNFalpha across the umbilical circulation in term pregnancies: relationship with labour events.. Early Hum Dev 2010;86(2):113-117.
  30. Kitajima H, Nakayama M, Miyano A. Significance of chorioamnionitis.. Early Hum Dev 1992;29(1-3):125-130.
  31. Scheller J, Chalaris A, Schmidt-Arras D, Rose-John S. The pro- and anti-inflammatory properties of the cytokine interleukin-6.. Biochim Biophys Acta 2011;1813(5):878-888.
  32. Rose-John S. Interleukin-6 biology is coordinated by membrane-bound and soluble receptors: role in inflammation and cancer.. J Leukoc Biol 2006;80(2):227-236.
  33. Rose-John S, Waetzig GH, Scheller J, Grötzinger J, Seegert D. The IL-6/sIL-6R complex as a novel target for therapeutic approaches.. Expert Opin Ther Targets 2007;11(5):613-624.
  34. Chalaris A, Garbers C, Rabe B, Rose-John S, Scheller J. The soluble Interleukin 6 receptor: generation and role in inflammation and cancer.. Eur J Cell Biol 2011;90(6-7):484-494.
  35. Romero R, Chaemsaithong P, Chaiyasit N. CXCL10 and IL-6: markers of two different forms of intra-amniotic inflammation in preterm labor.. Am J Reprod Immunol 2017;78(1).
  36. Rogers BB, Alexander JM, Head J, McIntire D, Leveno KJ. Umbilical vein interleukin-6 levels correlate with the severity of placental inflammation and gestational age.. Hum Pathol 2002;33(3):335-340.
  37. Ginther OJE. Pregnancy: Physical Interactions Between the Uterus and Conceptus.. in Am Assoc Equi Pract Baltimore, MD: IVIS; 1998.
  38. El-Sheikh Ali H, Boakari YL, Loux SC. Transcriptomic analysis of equine placenta reveals key regulators and pathways involved in ascending placentitis.. Biol Reprod 2020;102(6):1306-1325.
  39. Wagner B, Freer H. Development of a bead-based multiplex assay for simultaneous quantification of cytokines in horses.. Vet Immunol Immunopathol 2009;127(3-4):242-248.
  40. Skogstrand K. Multiplex assays of inflammatory markers, a description of methods and discussion of precautions - Our experience through the last ten years.. Methods 2012;56(2):204-212.
  41. Dobin A, Gingeras TR. Mapping RNA-seq Reads with STAR.. Curr Protoc Bioinformatics 2015;51:11.14.1-11.14.19.
  42. Trapnell C, Roberts A, Goff L. Differential gene and transcript expression analysis of RNA-seq experiments with TopHat and Cufflinks.. Nat Protoc 2012;7(3):562-578.
  43. Eulenfeld R, Dittrich A, Khouri C. Interleukin-6 signalling: more than Jaks and STATs.. Eur J Cell Biol 2012;91(6-7):486-495.
  44. Schaper F, Rose-John S. Interleukin-6: biology, signaling and strategies of blockade.. Cytokine Growth Factor Rev 2015;26(5):475-487.
  45. Fedorka CE, Loux SL, Scoggin KE, Adams AA, Troedsson MHT, Ball BA. Alterations in T cell-related transcripts at the feto-maternal interface throughout equine gestation.. Placenta 2019;89:78-87.
  46. Ali HE, Boakari YL, Loux SC. Transcriptomic analysis reveals the key regulators and molecular mechanisms underlying myometrial activation during equine placentitis.. Biol Reprod 2020;102:1306-1325.
  47. El-Sheikh Ali H, Legacki EL, Loux SC. Equine placentitis is associated with a downregulation in myometrial progestin signalingdagger.. Biol Reprod 2019;101:162-176.
  48. Moco NP, Martin LF, Pereira AC. Gene expression and protein localization of TLR-1, -2, -4 and -6 in amniochorion membranes of pregnancies complicated by histologic chorioamnionitis.. Eur J Obstet Gynecol Reprod Biol 2013;171(1):12-17.
  49. Waring GJ, Robson SC, Bulmer JN, Tyson-Capper AJ. Inflammatory signalling in fetal membranes: increased expression levels of TLR 1 in the presence of preterm histological chorioamnionitis.. PLoS One 2015;10(5):e0124298.
  50. Kim CJ, Romero R, Chaemsaithong P, Chaiyasit N, Yoon BH, Kim YM. Acute chorioamnionitis and funisitis: definition, pathologic features, and clinical significance.. Am J Obstet Gynecol 2015;213(4 Suppl):S29-S52.
  51. Musilova I, Kacerovsky M, Stepan M. Maternal serum C-reactive protein concentration and intra-amniotic inflammation in women with preterm prelabor rupture of membranes.. PLoS One 2017;12(8):e0182731.
  52. Samejima T, Takechi K. Elevated C-reactive protein levels in histological chorioamnionitis at term: impact of funisitis on term neonates.. J Matern Fetal Neonatal Med 2017;30(12):1428-1433.
  53. Gomez-Lopez N, Romero R, Leng Y. Neutrophil extracellular traps in acute chorioamnionitis: a mechanism of host defense.. Am J Reprod Immunol 2017;77(3).
  54. Gomez-Lopez N, Romero R, Yi X. Neutrophil extracellular traps in the amniotic cavity of women with intra-amniotic infection: a new mechanism of host defense.. Reprod Sci 2017;24(8):1139-1153.
  55. Hong CB, Donahue JM, Giles RC Jr. Etiology and pathology of equine placentitis.. J Vet Diagn Invest 1993;5(1):56-63.
  56. McGlothlin JA, Lester GD, Hansen PJ. Alteration in uterine contractility in mares with experimentally induced placentitis.. Reproduction 2004;127(1):57-66.
  57. Presicce P, Park CW, Senthamaraikannan P. IL-1 signaling mediates intrauterine inflammation and chorio-decidua neutrophil recruitment and activation.. JCI Insight 2018;3(6):e98306.
  58. Jacobsson B, Mattsby-Baltzer I, Hagberg H. Interleukin-6 and interleukin-8 in cervical and amniotic fluid: relationship to microbial invasion of the chorioamniotic membranes.. BJOG 2005;112(6):719-724.
  59. Romero R, Sepulveda W, Kenney JS, Archer LE, Allison AC, Sehgal PB. Interleukin 6 determination in the detection of microbial invasion of the amniotic cavity.. Ciba Found Symp 1992;167:205-220; discussion 220-3.
  60. Loux SC, Fernandes CB, Dini P. Small RNA (sRNA) expression in the chorioallantois, endometrium and serum of mares following experimental induction of placentitis.. Reprod Fertil Dev 2019;31:1144-1156.
  61. Hafez S. Comparative placental anatomy: divergent structures serving a common purpose.. Prog Mol Biol Transl Sci 2017;145:1-28.
  62. Canisso I, Barry Ball E, Squires MT. How to perform transabdominal ultrasound-guided fetal fluid sampling in the mare.. J Equine Vet Sci 2014;34:13.
  63. Schmidt AR, Williams MA, Carleton CL, Darien BJ, Derksen FJ. Evaluation of transabdominal ultrasound-guided amniocentesis in the late gestational mare.. Equine Vet J 1991;23(4):261-265.
  64. Cobo T, Kacerovsky M, Jacobsson B. Noninvasive sampling of the intrauterine environment in women with preterm labor and intact membranes.. Fetal Diagn Ther 2017;43(4):241-249.
  65. Mullberg J, Oberthür W, Lottspeich F. The soluble human IL-6 receptor. Mutational characterization of the proteolytic cleavage site.. J Immunol 1994;152(10):4958-4968.
  66. Edwards DR, Handsley MM, Pennington CJ. The ADAM metalloproteinases.. Mol Aspects Med 2008;29(5):258-289.
  67. Asati V, Mahapatra DK, Bharti SK. PI3K/Akt/mTOR and Ras/Raf/MEK/ERK signaling pathways inhibitors as anticancer agents: structural and pharmacological perspectives.. Eur J Med Chem 2016;109:314-341.
  68. Mihara M, Hashizume M, Yoshida H, Suzuki M, Shiina M. IL-6/IL-6 receptor system and its role in physiological and pathological conditions.. Clin Sci (Lond) 2012;122(4):143-159.
  69. Wolf J, Rose-John S, Garbers C. Interleukin-6 and its receptors: a highly regulated and dynamic system.. Cytokine 2014;70(1):11-20.
  70. Jones SA, Scheller J, Rose-John S. Therapeutic strategies for the clinical blockade of IL-6/gp130 signaling.. J Clin Invest 2011;121(9):3375-3383.
  71. Czabotar PE, Lessene G, Strasser A, Adams JM. Control of apoptosis by the BCL-2 protein family: implications for physiology and therapy.. Nat Rev Mol Cell Biol 2014;15(1):49-63.
  72. Baumann H, Gauldie J. The acute phase response.. Immunol Today 1994;15(2):74-80.
  73. Hoge J, Yan I, Jänner N. IL-6 controls the innate immune response against Listeria monocytogenes via classical IL-6 signaling.. J Immunol 2013;190(2):703-711.
  74. Lucke K, Yan I, Krohn S. Control of Listeria monocytogenes infection requires classical IL-6 signaling in myeloid cells.. PLoS One 2018;13(8):e0203395.
  75. Atreya R, Mudter J, Finotto S. Blockade of interleukin 6 trans signaling suppresses T-cell resistance against apoptosis in chronic intestinal inflammation: evidence in crohn disease and experimental colitis in vivo.. Nat Med 2000;6(5):583-588.
  76. Chalaris A, Rabe B, Paliga K. Apoptosis is a natural stimulus of IL6R shedding and contributes to the proinflammatory trans-signaling function of neutrophils.. Blood 2007;110(6):1748-1755.
  77. Diehl S, Rincon M. The two faces of IL-6 on Th1/Th2 differentiation.. Mol Immunol 2002;39(9):531-536.
  78. Sofi MH, Li W, Kaplan MH, Chang CH. Elevated IL-6 expression in CD4 T cells via PKCtheta and NF-kappaB induces Th2 cytokine production.. Mol Immunol 2009;46(7):1443-1450.
  79. Maeda Y, Ohtsuka H, Tomioka M. Effect of progesterone on Th1/Th2/Th17 and regulatory T cell-related genes in peripheral blood mononuclear cells during pregnancy in cows.. Vet Res Commun 2013;37(1):43-49.
  80. Makhseed M, Raghupathy R, Azizieh F. Th1 and Th2 cytokine profiles in recurrent aborters with successful pregnancy and with subsequent abortions.. Hum Reprod 2001;16(10):2219-2226.
  81. Piccinni MP. T cells in normal pregnancy and recurrent pregnancy loss.. Reprod Biomed Online 2006;13(6):840-844.
  82. Raghupathy R, Makhseed M, Azizieh F, Hassan N, Al-Azemi M, Al-Shamali E. Maternal Th1- and Th2-type reactivity to placental antigens in normal human pregnancy and unexplained recurrent spontaneous abortions.. Cell Immunol 1999;196(2):122-130.
  83. Saito S, Nakashima A, Shima T, Ito M. Th1/Th2/Th17 and regulatory T-cell paradigm in pregnancy.. Am J Reprod Immunol 2010;63(6):601-610.
  84. Oberg HH, Wesch D, Grüssel S, Rose-John S, Kabelitz D. Differential expression of CD126 and CD130 mediates different STAT-3 phosphorylation in CD4+CD25- and CD25high regulatory T cells.. Int Immunol 2006;18(4):555-563.
  85. Zhao S, Gu Y, Dong Q, Fan R, Wang Y. Altered interleukin-6 receptor, IL-6R and gp130, production and expression and decreased SOCS-3 expression in placentas from women with pre-eclampsia.. Placenta 2008;29(12):1024-1028.
  86. Dame JB, Juul SE. The distribution of receptors for the pro-inflammatory cytokines interleukin (IL)-6 and IL-8 in the developing human fetus.. Early Hum Dev 2000;58(1):25-39.
  87. Hsiao EY, Patterson PH. Activation of the maternal immune system induces endocrine changes in the placenta via IL-6.. Brain Behav Immun 2011;25(4):604-615.
  88. Canisso IF, Loux SC, Lima FS. Biomarkers for placental disease in mares.. Theriogenology 2020;150:302-307.

Citations

This article has been cited 6 times.
  1. Rosario FJ, Kelly AC, Gupta MB, Powell TL, Cox L, Jansson T. Mechanistic Target of Rapamycin Complex 2 Regulation of the Primary Human Trophoblast Cell Transcriptome. Front Cell Dev Biol 2021;9:670980.
    doi: 10.3389/fcell.2021.670980pubmed: 34805133google scholar: lookup
  2. Satué K, La Fauci D, Medica P, Damiá Gímenez E, Cravana C, Fazio E. Shifts between pro-inflammatory and anti-inflammatory profiles in pregnant mares: a review of physiological functions. Front Vet Sci 2025;12:1660759.
    doi: 10.3389/fvets.2025.1660759pubmed: 41049139google scholar: lookup
  3. Marchio SP, El-Sheikh Ali H, Scott MA, Barbosa Fernandes C, Scoggin KE, Troedsson M, Boakari Y. Decoding the amniotic membrane transcriptome during equine ascending placentitis. Sci Rep 2025 Aug 21;15(1):30714.
    doi: 10.1038/s41598-025-16671-5pubmed: 40841585google scholar: lookup
  4. Mu S, Shen Y, Ren H, Ulaangerel T, Yi M, Zhao B, Hao A, Liu Q, Wen X, Dugarjaviin M, Bou G. Effects of Interleukin-6 (IL-6) on In Vitro Cultured Equine Chorionic Girdle Cells. Animals (Basel) 2025 Feb 6;15(3).
    doi: 10.3390/ani15030450pubmed: 39943220google scholar: lookup
  5. Deng L, Jin Y, Zheng X, Yang Y, Feng Y, Zhou H, Zeng Q. Pharmacological and toxicological characteristics of baicalin in preventing spontaneous abortion and recurrent pregnancy loss: A multi-level critical review. Heliyon 2024 Oct 30;10(20):e38633.
    doi: 10.1016/j.heliyon.2024.e38633pubmed: 39640688google scholar: lookup
  6. Hobbs KJ, Bayless R, Sheats MK. A Comparative Review of Cytokines and Cytokine Targeting in Sepsis: From Humans to Horses. Cells 2024 Sep 5;13(17).
    doi: 10.3390/cells13171489pubmed: 39273060google scholar: lookup
Subscribe to our newsletter
Join 99,383 horse owners like you who receive our email updates on horse health and nutrition.