title: Interleukin-15 is required for maximal lipopolysaccharide-induced abortion.
abstract: The maternal immune response during pregnancy is critical for the survival of the fetus yet can be detrimental during infection and inflammation. Previously, IL-15 has been observed to mediate inflammation during LPS-induced sepsis. Therefore, we sought to determine whether IL-15 mediates the inflammatory process during LPS-induced abortion through the use of IL-15(-/-) and WT mice. Administration of 2.5 μg LPS i.p. on gd 7.5 drastically reduced fetal viability in WT mice, whereas it had a minimal effect on fetal survival in IL-15(-/-) mice. The uteroplacental sites of LPS-treated WT mice were characterized by vast structural degradation and inflammation compared with treated IL-15(-/-) and untreated controls. This suggests that IL-15 may mediate the inflammation responsible for LPS-induced resorption. As IL-15(-/-) mice are deficient in NK cells and resistant to LPS-induced abortion, these effects suggest that IL-15 may mediate abortion through their homeostatic and/or activation effects on NK cells. WT uteroplacental units exposed to LPS had an increase in the overall number and effector number of NK cells compared with their control counterparts. Furthermore, NK cell depletion before administration of LPS in WT mice partially restored fetal viability. Overall, this paper suggests that IL-15 mediates the inflammatory environment during LPS-induced fetal resorption, primarily through its effects on NK cells.
authors.affiliation: Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Lee
authors.forename: Nalaayini
authors.initials: N
authors.lastname: Kandiah
authors.forename: Khalil
authors.initials: K
authors.lastname: Karimi
authors.forename: David A
authors.initials: DA
authors.lastname: Clark
authors.forename: Ali A
authors.initials: AA
authors.lastname: Ashkar
mesh_terms: D000022:Abortion, Spontaneous / Q000139:chemically induced / Q000276:immunology*; D000818:Animals; D005260:Female; D005327:Fetal Resorption / Q000139:chemically induced / Q000276:immunology*; D005434:Flow Cytometry; D019409:Interleukin-15 / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology; D008070:Lipopolysaccharides / Q000633:toxicity; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011247:Pregnancy / Q000276:immunology*
chemical_list: D019409:Interleukin-15; D008070:Lipopolysaccharides
keywords: fetal resorption; miscarriage; natural killer cell