title: IL-18 is present at the maternal-fetal interface and enhances cytotoxic activity of decidual lymphocytes.
abstract: OBJECTIVE
  Perforin expressing uterine natural killer (uNK) cells are under complex cytokine influence. The aim of the study was to investigate the presence and role of interleukin (IL)-18 on NK cytolytic potential at maternal-fetal (M-F) interface.
  
  
  METHODS
  Peripheral blood cells and decidual tissue were obtained from elective pregnancy termination of normal human 6-10-week-old pregnancies. Perforin expression and cytolytic activity of peripheral blood (PBL) and decidual lymphocytes (DL) were analyzed by flow cytometry. IL-18 positive decidual adherent cells (DAC) were detected by the same method. Interleukin-18 and IL-18 receptor (IL-18R) expression on the trophoblastic cells was detected by immunohistology using biotinylated anti-IL-18 and IL-18R monoclonal antibodies.
  
  
  RESULTS
  The IL-18 added in a dose of 10 ng/mL up-regulates perforin expression and cytolytic activity of DL. Simultaneous stimulation with IL-18 and IL-12 enhanced DL cytolytic activity, while IL-18 combined with IL-10 or IL-15 did not show this effect. Cytolytic activity of PBL was up-regulated by IL-18 as well, and this effect was enhanced by the addition of IL-12 and IL-15. Interleukin-18 did not affect perforin-protein expression in cultured PBL. Approximately 20% of DAC were IL-18 positive and these cells were mostly human leukocyte antigen (HLA)-DR negative. IL-18R positive cells were found on syncytiotrophoblast cell layer, interstitial tissue cells of villi and fetal blood cells. There was no detectable IL-18 staining on trophoblast cell layer on villi, but strong staining of fetal blood cells in villous vessels.
  
  
  CONCLUSIONS
  These are first results showing IL-18R expression, but not IL-18 expression on villous trophoblastic cells, as well as enhancement of perforin expression and NK cytolytic potential of DL under the influence of IL-18. IL-18 in concert with other cytokines and hormones could play an important role in the regulation of cytolytic potential of first trimester pregnancy decidual and peripheral blood NK cells.
authors.affiliation: Department of Physiology and Immunology, Medical Faculty, University of Rijeka, Rijeka, Croatia.
authors.forename: Vlatka S
authors.initials: VS
authors.lastname: Tokmadzić
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Tsuji
authors.forename: Tatjana
authors.initials: T
authors.lastname: Bogović
authors.forename: Gordana
authors.initials: G
authors.lastname: Laskarin
authors.forename: Kristijan
authors.initials: K
authors.lastname: Cupurdija
authors.forename: Natasa
authors.initials: N
authors.lastname: Strbo
authors.forename: Koji
authors.initials: K
authors.lastname: Koyama
authors.forename: Haruki
authors.initials: H
authors.lastname: Okamura
authors.forename: Eckhard R
authors.initials: ER
authors.lastname: Podack
authors.forename: Daniel
authors.initials: D
authors.lastname: Rukavina
mesh_terms: D000328:Adult; D002824:Chorionic Villi / Q000378:metabolism; D003656:Decidua / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D020382:Interleukin-18 / Q000378:metabolism*; D007378:Interleukins / Q000378:metabolism; D007694:Killer Cells, Natural / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D011247:Pregnancy
chemical_list: D020382:Interleukin-18; D007378:Interleukins; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D054353:Perforin