Responses of the spleen to intra-amniotic lipopolysaccharide (LPS) exposure in fetal sheep

E Kuypers, MGM Willems, RK Jellema, Matthew Kemp, John Newnham, T Delhaas, Suhas Kallapur, Alan Jobe, TGAM Wolfs, Boris Kramer

    Research output: Contribution to journalArticle

    7 Citations (Scopus)

    Abstract

    Background:

    Intrauterine inflammation activates the fetal immune system and can result in organ injury and postnatal complications in preterm infants. As the spleen is an important site for peripheral immune activation, we asked how the fetal spleen would respond to intrauterine inflammation over time. We hypothesized that intraamniotic lipopolysaccharide (IA LPS) exposure induces acute and persistent changes in the splenic cytokine profile and T-cell composition that may contribute to the sustained fetal inflammatory response after chorioamnionitis.

    Methods:

    Fetal sheep were exposed to IA LPS 5, 12, and 24 h and 2, 4, 8, or 15 d before delivery at 125 d of gestational age (term = 150 d). Splenic cytokine mRNA levels and cleaved caspase-3, CD3, and Foxp3 expression were evaluated.

    Results:

    IA LPS increased interleukin (IL)1, IL4, IL5, and IL10 mRNA by twofold 24 h after injection. Interferon gamma increased by fivefold, whereas IL23 decreased 15 d post-LPS exposure. Cleaved caspase-3–positive cells increased 2 and 8 d after LPS exposure. CD3 immunoreactivity increased within 5 h with increased Foxp3-postive cells at 12 h.

    Conclusion:

    Intrauterine inflammation induced a rapid and sustained splenic immune response with persistent changes in the cytokine profile. This altered immune status may drive sustained inflammation and injury in other fetal organs.
    Original languageEnglish
    Pages (from-to)29–35
    JournalPediatric Research
    Volume77
    DOIs
    Publication statusPublished - 2015

    Fingerprint

    Lipopolysaccharides
    Sheep
    Spleen
    Inflammation
    Cytokines
    Chorioamnionitis
    Messenger RNA
    Interleukin-5
    Wounds and Injuries
    Caspases
    Interleukin-1
    Premature Infants
    Caspase 3
    Interleukin-4
    Interleukin-10
    Gestational Age
    Interferon-gamma
    Immune System
    T-Lymphocytes
    Injections

    Cite this

    Kuypers, E ; Willems, MGM ; Jellema, RK ; Kemp, Matthew ; Newnham, John ; Delhaas, T ; Kallapur, Suhas ; Jobe, Alan ; Wolfs, TGAM ; Kramer, Boris. / Responses of the spleen to intra-amniotic lipopolysaccharide (LPS) exposure in fetal sheep. In: Pediatric Research. 2015 ; Vol. 77. pp. 29–35.
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    title = "Responses of the spleen to intra-amniotic lipopolysaccharide (LPS) exposure in fetal sheep",
    abstract = "Background:Intrauterine inflammation activates the fetal immune system and can result in organ injury and postnatal complications in preterm infants. As the spleen is an important site for peripheral immune activation, we asked how the fetal spleen would respond to intrauterine inflammation over time. We hypothesized that intraamniotic lipopolysaccharide (IA LPS) exposure induces acute and persistent changes in the splenic cytokine profile and T-cell composition that may contribute to the sustained fetal inflammatory response after chorioamnionitis.Methods:Fetal sheep were exposed to IA LPS 5, 12, and 24 h and 2, 4, 8, or 15 d before delivery at 125 d of gestational age (term = 150 d). Splenic cytokine mRNA levels and cleaved caspase-3, CD3, and Foxp3 expression were evaluated.Results:IA LPS increased interleukin (IL)1, IL4, IL5, and IL10 mRNA by twofold 24 h after injection. Interferon gamma increased by fivefold, whereas IL23 decreased 15 d post-LPS exposure. Cleaved caspase-3–positive cells increased 2 and 8 d after LPS exposure. CD3 immunoreactivity increased within 5 h with increased Foxp3-postive cells at 12 h.Conclusion:Intrauterine inflammation induced a rapid and sustained splenic immune response with persistent changes in the cytokine profile. This altered immune status may drive sustained inflammation and injury in other fetal organs.",
    author = "E Kuypers and MGM Willems and RK Jellema and Matthew Kemp and John Newnham and T Delhaas and Suhas Kallapur and Alan Jobe and TGAM Wolfs and Boris Kramer",
    year = "2015",
    doi = "10.1038/pr.2014.152",
    language = "English",
    volume = "77",
    pages = "29–35",
    journal = "Pediatric Research: international journal of human developmental biology",
    issn = "0031-3998",
    publisher = "INT PEDIATRIC RESEARCH FOUNDATION, INC",

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    Kuypers, E, Willems, MGM, Jellema, RK, Kemp, M, Newnham, J, Delhaas, T, Kallapur, S, Jobe, A, Wolfs, TGAM & Kramer, B 2015, 'Responses of the spleen to intra-amniotic lipopolysaccharide (LPS) exposure in fetal sheep' Pediatric Research, vol. 77, pp. 29–35. https://doi.org/10.1038/pr.2014.152

    Responses of the spleen to intra-amniotic lipopolysaccharide (LPS) exposure in fetal sheep. / Kuypers, E; Willems, MGM; Jellema, RK; Kemp, Matthew; Newnham, John; Delhaas, T; Kallapur, Suhas; Jobe, Alan; Wolfs, TGAM; Kramer, Boris.

    In: Pediatric Research, Vol. 77, 2015, p. 29–35.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - Responses of the spleen to intra-amniotic lipopolysaccharide (LPS) exposure in fetal sheep

    AU - Kuypers, E

    AU - Willems, MGM

    AU - Jellema, RK

    AU - Kemp, Matthew

    AU - Newnham, John

    AU - Delhaas, T

    AU - Kallapur, Suhas

    AU - Jobe, Alan

    AU - Wolfs, TGAM

    AU - Kramer, Boris

    PY - 2015

    Y1 - 2015

    N2 - Background:Intrauterine inflammation activates the fetal immune system and can result in organ injury and postnatal complications in preterm infants. As the spleen is an important site for peripheral immune activation, we asked how the fetal spleen would respond to intrauterine inflammation over time. We hypothesized that intraamniotic lipopolysaccharide (IA LPS) exposure induces acute and persistent changes in the splenic cytokine profile and T-cell composition that may contribute to the sustained fetal inflammatory response after chorioamnionitis.Methods:Fetal sheep were exposed to IA LPS 5, 12, and 24 h and 2, 4, 8, or 15 d before delivery at 125 d of gestational age (term = 150 d). Splenic cytokine mRNA levels and cleaved caspase-3, CD3, and Foxp3 expression were evaluated.Results:IA LPS increased interleukin (IL)1, IL4, IL5, and IL10 mRNA by twofold 24 h after injection. Interferon gamma increased by fivefold, whereas IL23 decreased 15 d post-LPS exposure. Cleaved caspase-3–positive cells increased 2 and 8 d after LPS exposure. CD3 immunoreactivity increased within 5 h with increased Foxp3-postive cells at 12 h.Conclusion:Intrauterine inflammation induced a rapid and sustained splenic immune response with persistent changes in the cytokine profile. This altered immune status may drive sustained inflammation and injury in other fetal organs.

    AB - Background:Intrauterine inflammation activates the fetal immune system and can result in organ injury and postnatal complications in preterm infants. As the spleen is an important site for peripheral immune activation, we asked how the fetal spleen would respond to intrauterine inflammation over time. We hypothesized that intraamniotic lipopolysaccharide (IA LPS) exposure induces acute and persistent changes in the splenic cytokine profile and T-cell composition that may contribute to the sustained fetal inflammatory response after chorioamnionitis.Methods:Fetal sheep were exposed to IA LPS 5, 12, and 24 h and 2, 4, 8, or 15 d before delivery at 125 d of gestational age (term = 150 d). Splenic cytokine mRNA levels and cleaved caspase-3, CD3, and Foxp3 expression were evaluated.Results:IA LPS increased interleukin (IL)1, IL4, IL5, and IL10 mRNA by twofold 24 h after injection. Interferon gamma increased by fivefold, whereas IL23 decreased 15 d post-LPS exposure. Cleaved caspase-3–positive cells increased 2 and 8 d after LPS exposure. CD3 immunoreactivity increased within 5 h with increased Foxp3-postive cells at 12 h.Conclusion:Intrauterine inflammation induced a rapid and sustained splenic immune response with persistent changes in the cytokine profile. This altered immune status may drive sustained inflammation and injury in other fetal organs.

    U2 - 10.1038/pr.2014.152

    DO - 10.1038/pr.2014.152

    M3 - Article

    VL - 77

    SP - 29

    EP - 35

    JO - Pediatric Research: international journal of human developmental biology

    JF - Pediatric Research: international journal of human developmental biology

    SN - 0031-3998

    ER -