Intravenous lipopolysaccharide-induced pulmonary maturation and structural changes in fetal sheep

Boris W. Kramer; Andreas Ladenburger; Steffen Kunzmann; Christian P. Speer; Jasper V. Been; J. Freek van Iwaarden; Luc J.I. Zimmermann; Markus Gantert; Yves Garnier

doi:10.1016/j.ajog.2008.09.009

Intravenous lipopolysaccharide-induced pulmonary maturation and structural changes in fetal sheep

Boris W. Kramer^*, Andreas Ladenburger, Steffen Kunzmann, Christian P. Speer, Jasper V. Been, J. Freek van Iwaarden, Luc J.I. Zimmermann, Markus Gantert, Yves Garnier

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

38 Citations (Scopus)

Abstract

Background: Antenatal pulmonary inflammation is associated with reduced risk for respiratory distress syndrome but with an increased risk for bronchopulmonary dysplasia (BPD) with impaired alveogenesis. Objective: We hypothesized that fetal systemic inflammation induced by intravenous (IV) lipopolysaccharide (LPS) would affect lung development in utero. Study Design: Twenty-one fetal sheep were instrumented (107 days gestational age). Control fetuses received saline (N = 12) and 9 in the study group received 100 ng of LPS IV 3 days after surgery. Animals were assessed for lung maturation and structure after 3 (N = 5) and 7 (N = 4) days. Results: Interleukin-6 concentration increased in the bronchoalveolar lavage more than 40-fold 3 days after LPS IV. Processing of pro-surfactant protein (SP)-B to mature SP-B and increased SP-B concentrations were shown 7 days after LPS IV. Deposition of elastin fibers at sites of septation was disturbed within 3 days after LPS IV. Conclusion: Lung maturation and disturbed lung structure occurred after short-term exposure to fetal inflammation and suggests new targeted therapies for BPD.

Original language	English
Pages (from-to)	195.e1-195.e10
Journal	American Journal of Obstetrics and Gynecology
Volume	200
Issue number	2
DOIs	https://doi.org/10.1016/j.ajog.2008.09.009
Publication status	Published - Feb 2008
Externally published	Yes

Bibliographical note

Funding Information:
Supported by the Interdisciplinary Center for Clinical Research, Wuerzburg, Germany, Grant A-27; the Universitätsbund Würzburg, the Schuster Stiftung, Frankfurt a.M., Germany; and the Stichting Kindergeneeskunde, and Research School GROW, University of Maastricht, Maastricht, the Netherlands.

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10.1016/j.ajog.2008.09.009

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title = "Intravenous lipopolysaccharide-induced pulmonary maturation and structural changes in fetal sheep",

abstract = "Background: Antenatal pulmonary inflammation is associated with reduced risk for respiratory distress syndrome but with an increased risk for bronchopulmonary dysplasia (BPD) with impaired alveogenesis. Objective: We hypothesized that fetal systemic inflammation induced by intravenous (IV) lipopolysaccharide (LPS) would affect lung development in utero. Study Design: Twenty-one fetal sheep were instrumented (107 days gestational age). Control fetuses received saline (N = 12) and 9 in the study group received 100 ng of LPS IV 3 days after surgery. Animals were assessed for lung maturation and structure after 3 (N = 5) and 7 (N = 4) days. Results: Interleukin-6 concentration increased in the bronchoalveolar lavage more than 40-fold 3 days after LPS IV. Processing of pro-surfactant protein (SP)-B to mature SP-B and increased SP-B concentrations were shown 7 days after LPS IV. Deposition of elastin fibers at sites of septation was disturbed within 3 days after LPS IV. Conclusion: Lung maturation and disturbed lung structure occurred after short-term exposure to fetal inflammation and suggests new targeted therapies for BPD.",

author = "Kramer, {Boris W.} and Andreas Ladenburger and Steffen Kunzmann and Speer, {Christian P.} and Been, {Jasper V.} and {van Iwaarden}, {J. Freek} and Zimmermann, {Luc J.I.} and Markus Gantert and Yves Garnier",

note = "Funding Information: Supported by the Interdisciplinary Center for Clinical Research, Wuerzburg, Germany, Grant A-27; the Universit{\"a}tsbund W{\"u}rzburg, the Schuster Stiftung, Frankfurt a.M., Germany; and the Stichting Kindergeneeskunde, and Research School GROW, University of Maastricht, Maastricht, the Netherlands. ",

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doi = "10.1016/j.ajog.2008.09.009",

language = "English",

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T1 - Intravenous lipopolysaccharide-induced pulmonary maturation and structural changes in fetal sheep

AU - Kramer, Boris W.

AU - Ladenburger, Andreas

AU - Kunzmann, Steffen

AU - Speer, Christian P.

AU - Been, Jasper V.

AU - van Iwaarden, J. Freek

AU - Zimmermann, Luc J.I.

AU - Gantert, Markus

AU - Garnier, Yves

N1 - Funding Information: Supported by the Interdisciplinary Center for Clinical Research, Wuerzburg, Germany, Grant A-27; the Universitätsbund Würzburg, the Schuster Stiftung, Frankfurt a.M., Germany; and the Stichting Kindergeneeskunde, and Research School GROW, University of Maastricht, Maastricht, the Netherlands.

PY - 2008/2

Y1 - 2008/2

N2 - Background: Antenatal pulmonary inflammation is associated with reduced risk for respiratory distress syndrome but with an increased risk for bronchopulmonary dysplasia (BPD) with impaired alveogenesis. Objective: We hypothesized that fetal systemic inflammation induced by intravenous (IV) lipopolysaccharide (LPS) would affect lung development in utero. Study Design: Twenty-one fetal sheep were instrumented (107 days gestational age). Control fetuses received saline (N = 12) and 9 in the study group received 100 ng of LPS IV 3 days after surgery. Animals were assessed for lung maturation and structure after 3 (N = 5) and 7 (N = 4) days. Results: Interleukin-6 concentration increased in the bronchoalveolar lavage more than 40-fold 3 days after LPS IV. Processing of pro-surfactant protein (SP)-B to mature SP-B and increased SP-B concentrations were shown 7 days after LPS IV. Deposition of elastin fibers at sites of septation was disturbed within 3 days after LPS IV. Conclusion: Lung maturation and disturbed lung structure occurred after short-term exposure to fetal inflammation and suggests new targeted therapies for BPD.

AB - Background: Antenatal pulmonary inflammation is associated with reduced risk for respiratory distress syndrome but with an increased risk for bronchopulmonary dysplasia (BPD) with impaired alveogenesis. Objective: We hypothesized that fetal systemic inflammation induced by intravenous (IV) lipopolysaccharide (LPS) would affect lung development in utero. Study Design: Twenty-one fetal sheep were instrumented (107 days gestational age). Control fetuses received saline (N = 12) and 9 in the study group received 100 ng of LPS IV 3 days after surgery. Animals were assessed for lung maturation and structure after 3 (N = 5) and 7 (N = 4) days. Results: Interleukin-6 concentration increased in the bronchoalveolar lavage more than 40-fold 3 days after LPS IV. Processing of pro-surfactant protein (SP)-B to mature SP-B and increased SP-B concentrations were shown 7 days after LPS IV. Deposition of elastin fibers at sites of septation was disturbed within 3 days after LPS IV. Conclusion: Lung maturation and disturbed lung structure occurred after short-term exposure to fetal inflammation and suggests new targeted therapies for BPD.

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Intravenous lipopolysaccharide-induced pulmonary maturation and structural changes in fetal sheep

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