title: Disruption of interleukin-18, but not interleukin-1, increases vulnerability to preterm delivery and fetal mortality after intrauterine inflammation.
abstract: Preterm birth is a major contributor of adverse perinatal outcome. Clinical data suggest that an inflammatory response is important in the process leading to preterm labor. By using a recently introduced mouse model of localized intrauterine lipopolysaccharide-induced inflammation, the effect of interleukin (IL)-18 gene disruption and/or IL-18 neutralization as well as combined IL-1alpha/beta gene disruption on inflammation-induced fetal loss was investigated. The frequency of preterm fetal loss was significantly higher in IL-18 knockout mice (58.9%) and in mice administered IL-18-binding protein (59.7%) compared to wild-type controls (34.7%). The rate of fetal loss was not affected by IL-1alpha/beta gene deficiency (38.7%). Decreased IL-18 protein expression combined with elevated IL-12 protein expression in uterine tissue of IL-18 knockout mice and IL-18-binding protein-treated animals was noticed. These data demonstrate that preterm pregnancy loss in response to intrauterine inflammation was enhanced by disruption of the IL-18 gene and/or IL-18 neutralization, events that may relate to exaggerated Th1 responses because of an increased IL-12/IL-18 ratio.
authors.affiliation: Perinatal Center, Department of Physiology, Göteborg University., Box 432, S-405 30 Göteborg, Sweden, and The Third Affiliated Hospital of Zhengzhou University, People's Republic of China. xiaoyang.wang@fysiologi.gu.se
authors.forename: Xiaoyang
authors.initials: X
authors.lastname: Wang
authors.forename: Henrik
authors.initials: H
authors.lastname: Hagberg
authors.forename: Carina
authors.initials: C
authors.lastname: Mallard
authors.forename: Changlian
authors.initials: C
authors.lastname: Zhu
authors.forename: Maj
authors.initials: M
authors.lastname: Hedtjärn
authors.forename: Carl-Fredrik
authors.initials: CF
authors.lastname: Tiger
authors.forename: Kristina
authors.initials: K
authors.lastname: Eriksson
authors.forename: Asa
authors.initials: A
authors.lastname: Rosen
authors.forename: Bo
authors.initials: B
authors.lastname: Jacobsson
mesh_terms: D000818:Animals; D005260:Female; D005313:Fetal Death / Q000139:chemically induced / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D006023:Glycoproteins / Q000276:immunology / Q000494:pharmacology; D007249:Inflammation / Q000139:chemically induced / Q000235:genetics / Q000276:immunology / Q000473:pathology; D036341:Intercellular Signaling Peptides and Proteins; D007375:Interleukin-1 / Q000172:deficiency* / Q000276:immunology; D018664:Interleukin-12 / Q000276:immunology; D020382:Interleukin-18 / Q000235:genetics* / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology / Q000633:toxicity; D051379:Mice; D018345:Mice, Knockout; D011247:Pregnancy; D018417:Th1 Cells / Q000276:immunology / Q000473:pathology; D014599:Uterus / Q000276:immunology / Q000473:pathology
chemical_list: D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; D007375:Interleukin-1; D020382:Interleukin-18; D008070:Lipopolysaccharides; C118370:interleukin-18 binding protein; D018664:Interleukin-12