Are There Any Differences Between the Distribution of Placental Bed Leukocyte Subtypes and Plasma Cytokine Levels of Preeclamptic and Healthy Pregnants?

Document Type : Original Articles

Authors

1 Department of Obstetrics and Gynecology, School of Medicine, Firat University, Elazığ, Turkey.

2 Department of Medical Services and Techniques, School of Health Services, Firat University, Elazığ, Turkey.

3 Department of Pathology, Faculty of Medicine, Inonu University, Malatya, Turkey.

4 Department of Immunology, School of Medicine, Firat University, Elazığ, Turkey.

Abstract

Objectives: Preeclampsia (PE) is associated with impaired decidual leukocyte and plasma cytokine balance compared with normal pregnancy. We aimed to investigate maternal plasma levels of Interferon-gamma (IFN-g), Tumor Necrosis Factor-alpha (TNF-a), Transforming Growth Factor-beta (TGF-b), Interleukin-4 (IL4), IL6, IL10, IL17, IL35, suppressor of Cytokine Signalling-3 (SOCS3) and placental bed leukocytes in preeclamptic and healthy pregnants.Materials & Methods: This study was conducted with 40 preeclamptic and 40 normotensive pregnants. Cytokine levels were studied with enzyme-linked immunosorbent assay. CD8, CD56 and CD163 antigens were analysed by immunohistochemical study on placental bed biopsies. Results: In preeclamptic women; IFN-g and TGF-b levels were significantly higher and IL-35 levels were significantly lower than those of controls. CD8, CD56 and CD163 positivity of preeclamptic group were not significantly higher than those of controls. CD8 staining showed negative correlation with plasma IL17 levels. CD163 staining showed negative correlation with TNF-a/IL4 ratio. TNF-a/IL4 ratio showed minimal influence on placental bed CD163 staining.Conclusion: Slightly increased placental bed CD8, CD56 and CD163 positive leukocytes and increased plasma IFN-g, TGF-b and decreased plasma IL35 levels of preeclamptic pregnants indicate an aberrant cell mediated immunity in PE. We could not say yet that this condition is whether result or reason. New studies are needed to discuss our results. 

Keywords

References

  1. Ahn H, Park J, Gilman-Sachs A, Kwak-Kim J. Immunologic characteristics of preeclampsia, a comprehensive review. American Journal of Reproductive Immunology. 2010; 65(4):377–94. doi: 10.1111/j.1600-0897.2010.00913.x
  2. Challis JR, Lockwood CJ, Myatt L, Norman JE, Strauss JF 3rd, Petraglia F. Inflammation and pregnancy. Reproductive Sciences. 2009; 16(2):206–15. doi: 10.1177/1933719108329095
  3. Sykes L, MacIntyre DA, Yap XJ, Teoh TG, Bennett PR. The Th1:th2 dichotomy of pregnancy and preterm labour. Mediators of Inflammation. 2012; 2012:1–12. doi: 10.1155/2012/967629
  4. Cemgil Arikan D, Aral M, Coskun A, Ozer A. Plasma IL-4, IL-8, IL-12, interferon-γ and CRP levels in pregnant women with preeclampsia, and their relation with severity of disease and fetal birth weight. Journal of Maternal-Fetal & Neonatal Medicine. 2012; 25(9):1569–73. doi: 10.3109/14767058.2011.648233
  5. Toldi G, Rigo J, Stenczer B, Vasarhelyi B, Molvarec A.. Increased prevalence of IL-17-producing peripheral blood lymphocytes in pre-eclampsia. American Journal of Reproductive Immunology. 2011; 66(3):223–9. doi: 10.1111/j.1600-0897.2011.00987.x.
  6. Darmochwal-Kolarz D, Kludka-Sternik M, Tabarkiewicz J, Kolarz B, Rolinski J, Leszczynska-Gorzelak B, et al. The predominance of Th17 lymphocytes and decreased number and function of Treg cells in preeclampsia. Journal of Reproductive Immunology. 2012; 93(2):75–81. doi: 10.1016/j.jri.2012.01.006
  7. Lau SY, Guild SJ, Barrett CJ, Chen Q, McCowan L, Jordan V, et al. Tumor necrosis factor-alpha, interleukin-6, and interleukin-10 levels are altered in preeclampsia: A systematic review and meta-analysis. American Journal of Reproductive Immunology. 2013; 70:412-27. doi: 10.1111/aji.12138
  8. Aki A, Abe M, Komaki M, Oku K, Iseki S, Mizutani S, et al. Expression of angiogenesis-related factors and inflammatory cytokines in placenta and umbilical vessels in pregnancies with preeclampsia and chorioamnionitis/funisitis. Congenital Anomalies. 2012; 52(2):97–103. doi: 10.1111/j.1741-4520.2012.00359.x
  9. Feizollahzadeh S, Taheripanah R, Khani M, Farokhi B, Amani D. Promoter region polymorphisms in the transforming growth factor beta-1 (TGFβ1) gene and serum TGFβ1 concentration in preeclamptic and control Iranian women. Journal of Reproductive Immunology. 2012; 94(2):216–21. doi: 10.1016/j.jri.2012.02.006
  10. Pinheiro MB, Martins-Filho OA, Mota APL, Alpoim PN, Godoi LC, Silveira ACO, et al. Severe preeclampsia goes along with a cytokine network disturbance towards a systemic inflammatory state. Cytokine. 2013; 62(1):165–73. doi: 10.1016/j.cyto.2013.02.027
  11. Pinheiro MB, Martins-Filho OA, Mota APL, Alpoim PN, Godoi LC, Silveira ACO, et al. Severe preeclampsia goes along with a cytokine network disturbance towards a systemic inflammatory state. Cytokine. 2013; 62(1):165–73. doi: 10.1016/j.cyto.2013.02.027
  12. Abell K, Watson CJ. The Jak/Stat pathway: A novel way to regulate PI3K activity. Cell Cycle. 2005; 4(7):897–900. doi: 10.4161/cc.4.7.1837
  13. Carow B, Reuschl A-K, Gavier-Widen D, Jenkins BJ, Ernst M, Yoshimura A, et al. Critical and independent role for socs3 in either myeloid or T-cells in resistance to mycobacterium tuberculosis. Public Library of Science. 2013; 9(7):1003442. doi: 10.1371/journal.ppat.1003442
  14. Bulmer JN, Sunderland CA. Immunohistological characterization of lymphoid cell populations in the early human placental bed. Immunology. 1984; 52(2):349-357. PMCID: PMC1454628
  15. Kabawat SE, Mostoufi-Zadeh M, Berkowitz RS, Driscoll SG, Goldstein DP, Bhan AK. Implantation site in complete molar pregnancy: A study of immunologically competen T-cells with monoclonal antibodies. American Journal of Obstetrics and Gynecology. 1985; 152(1):97–9. doi: 10.1016/s0002-9378(85)80188-5
  16. Lau SK, Chu PG, Weiss LM. CD163. A specific marker of macrophages in paraffin-embedded tissue samples. American Journal of Clinical Pathology. 2004; 122(5):794–801. doi: 10.1309/qhd6-yfn8-1kqx-uuh6
  17. Haller H, Radillo O, Rukavina D, Tedesco F, Candussi G, Petrović O, et al. An immunohistochemical study of leucocytes in human endometrium, first and third trimester basal decidua. Journal of Reproductive Immunology. 1993; 23(1):41–9. doi: 10.1016/0165-0378(93)90025-d
  18. Haller H, Tedesco F, Rukavina D, Radillo O, Gudelj L, Beer AE. Decidual-trophoblast interactions: decidual lymphoid cell populations in basal and parietal decidua. Journal of Reproductive Immunology. 1995; 28(2):165–71. doi: 10.1016/0165-0378(94)00913-r
  19. Sindram-Trujillo AP, Scherjon SA, van Hulst-van Miert PP, van Schip JJ, Kanhai HH, Roelen DL, Claas FH. Differential distribution of NK cells in decidua basalis compared with decidua parietalis after uncomplicated human term pregnancy. Human Immunol. 2003; 64(10):921-929. doi: 10.1016/s0198-8859(03)00170-8
  20. Lee CL, Guo Y, So KH, Vijayan M, Guo Y, Wong VHH, et al. Soluble human leukocyte antigen G5 polarizes differentiation of macrophages toward a decidual macrophage-like phenotype. Human Reproduction. 2015; 30(10):2263–74. doi: 10.1093/humrep/dev196
  21. Williams PJ, Bulmer JN, Searle RF, Innes BA, Robson SC. Altered decidual leucocyte populations in the placental bed in pre-eclampsia and foetal growth restriction: a comparison with late normal pregnancy. Reproduction. 2009; 138(1):177–84. doi: 10.1530/rep-09-0007
  22. Lockwood CJ, Matta P, Krikun G, Koopman LA, Masch R, Toti P, et al. Regulation of monocyte chemoattractant protein-1 expression by tumor necrosis factor-alpha and interleukin-1beta in first trimester human decidual cells: Implications for preeclampsia. The American Journal of Pathology. 2006; 168(2):445–52. doi: 10.2353/ajpath.2006.050082
  23. Kronborg CS, Gjedsted J, Vittinghus E, Hansen TK, Allen J, Knudsen UB. Longitudinal measurement of cytokines in pre-eclamptic and normotensive pregnancies. Acta Obstetricia et Gynecologica Scandinavica. 2011; 90(7):791-796. doi: 10.1111/j.1600-0412.2011.01134.x
  24. Tarnowska-Madra U, Leibschang J, Kowalska B, Filipp E, Kozar A, Nimer A, Maciejewski T. Levels of immunoreactive cytokines in serum of women with preeclampsia or severe pregnancy hypertension. Acta Obstetricia et Gynecologica Scandinavica. 2011; 90(7):791–6. doi: 10.1111/j.1600-0412.2011.01134.x
  25. Liu L, Zhao G, Fan H, Zhao X, Li P, Wang Z, Hu Y, Hou Y. Mesenchymal stem cells ameliorate Th1-induced pre-eclampsia-like symptoms in mice via the suppression of TNF-α expression. PLoS One. 2014; 9(2):88036. doi: 10.1371/journal.pone.0088036
  26. Olvarec A, Szarka A, Walentin S, Bekő G, Karadi I, Prohaszka Z, et al. Serum heat shock protein 70 levels in relation to circulating cytokines, chemokines, adhesion molecules and angiogenic factors in women with preeclampsia. Clinica Chimica Acta. 2011; 412(21-22):1957–62. doi: 10.1016/j.cca.2011.06.042
  27. Dhillion P, Wallace K, Herse F, Scott J, Wallukat G, Heath J, et al. IL-17-mediated oxidative stress is an important stimulator of AT1-AA and hypertension during pregnancy. AJP: Regulatory, Integrative and Comparative Physiology. 2012; 303(4):R353–R358. doi: 10.1152/ajpregu.00051.2012
  28. Mao H, Gao W, Ma C, Sun J, Liu J, Shao Q, et al. Human placental trophoblasts express the immunosuppressive cytokine IL-35. Human Immunology. 2013; 74(7):872–7. doi: 10.1016/j.humimm.2013.04.010
  29. Whitehead GS, Wilson RH, Nakano K, Burch LH, Nakano H, Cook DN. IL-35 production by inducible costimulator (ICOS)–positive regulatory T-cells reverses established IL-17–dependent allergic airways disease. Journal of Allergy and Clinical Immunology. 2012; 129(1):207–215.e5. doi: 10.1016/j.jaci.2011.08.009
  30. Niedbala W, Wei X, Cai B, Hueber AJ, Leung BP, McInnes IB, et al. IL-35 is a novel cytokine with therapeutic effects against collagen-induced arthritis through the expansion of regulatory T-cells and suppression of Th17 cells. European Journal of Immunology. 2007; 37(11):3021–9. doi: 10.1002/eji.200737810
  31. Ang MX, Hu XH, Liu ZZ, Kwak-Kim J, Liao AH. What are the roles of macrophages and monocytes in human pregnancy? Journal of Reproductive Immunology. 2015; 112:73–80. doi: 10.1016/j.jri.2015.08.001
  32. Rätsep MT, Felker AM, Kay VR, Tolusso L, Hofmann AP, Croy BA. Uterine natural killer cells: Supervisors of vasculature construction in early deciduabasalis. Reproduction. 2015; 149(2):91-102. doi: 10.1530/rep-14-0271
  33. Lima PD, Zhang J, Dunk C, Lye SJ, Anne Croy B. Leukocyte driven-decidual angiogenesis in early pregnancy. Cellular and Molecular Immunology. 2014; 11(6):522–37. doi: 10.1038/cmi.2014.63
  34. Lockwood CJ, Basar M, Kayisli UA, Guzeloglu-Kayisli O, Murk W, Wang J, et al. Interferon-γ protects first-trimester decidual cells against aberrant matrix metalloproteinases 1, 3, and 9 expression in preeclampsia. American Journal of Pathology. 2014; 184(9):2549–59. doi: 10.1016/j.ajpath.2014.05.025
  35. Sones JL, Lob HE, Isroff CE, Davisson RL. Role of decidual natural killer cells, interleukin-15, and interferon- in placental development and preeclampsia. AJP: Regulatory, Integrative and Comparative Physiology. 2014; 307(5):490–2. doi: 10.1152/ajpregu.00176.2014
  36. Sasaki Y, Darmochwal-Kolarz D, Suzuki D, Sakai M, Ito M, Shima T, et al. Proportion of peripheral blood and decidual CD4+ CD25 bright regulatory T-cells in pre-eclampsia. Clinical & Experimental Immunology. 2007; 149(1):139–45. doi: 10.1111/j.1365-2249.2007.03397.x
  37. Nakabayashi Y, Nakashima A, Yoshino O, Shima T, Shiozaki A, Adachi T, et al. Impairment of the accumulation of decidual T-cells, NK cells, and monocytes, and the poor vascular remodeling of spiral arteries, were observed in oocyte donation cases, regardless of the presence or absence of preeclampsia. Journal of Reproductive Immunology. 2016; 114:65–74. doi: 10.1016/j.jri.2015.07.005
  38. Wong AWY, Archer B, Mariee N, Li TC, Laird SM. Do uterine natural killer cell numbers in peri-implantation endometrium predict hypertensive disorder in pregnancy in women with a history of reproductive failure? Journal of Reproductive Immunology. 2014; 106:34–40. doi: 10.1016/j.jri.2014.04.005
  39. Lockwood CJ, Huang SJ, Chen CP, Huang Y, Xu J, Faramarzi S, et al. Decidual cell regulation of natural killer cell–recruiting chemokines. American Journal of Pathology. 2013; 183(3):841–56. doi: 10.1016/j.ajpath.2013.05.029
  40. Tang Z, Buhimschi IA, Buhimschi CS, Tadesse S, Norwitz E, Niven-Fairchild T, et al. Decreased levels of folate receptor-β and reduced numbers of fetal macrophages (Hofbauer cells) in placentas from pregnancies with severe pre-eclampsia. American Journal of Reproductive Immunology. 2013; 70(2):104–15. doi: 10.1111/aji.12112
  41. Medeiros LTL, Peracoli JC, Romao M, Bannwart-Castro CF, Golim MA, Borges VTM, et al. PP064. M1 Monocyte subpopulation is associated with pro-inflammatory cytokineproduction in pregnant women with preeclampsia. Pregnancy Hypertension: An International Journal of Women’s Cardiovascular Health. 2012; 2(3):276–7. doi: 10.1016/j.preghy.2012.04.175
  42. Kronborg CS, Breth Knudsen U, Moestrup SK, Allen J, Vittinghus E, Møller HJ. Serum markers of macrophage activation in pre-eclampsia: no predictive value of soluble CD163 and neopterin. Acta Obstetricia et Gynecologica Scandinavica. 2007; 86(9):1041–6. doi: 10.1080/00016340701415236
  43. Schonkeren D, van der Hoorn M-L, Khedoe P, Swings G, van Beelen E, Claas F, et al. Differential distribution and phenotype of decidual macrophages in preeclamptic versus control pregnancies. American Journal of Pathology. 2011; 178(2):709–17. doi: 10.1016/j.ajpath.2010.10.011

Files

Share

How to cite

Statistics