Endotoxin-induced chorioamnionitis modulates innate immunity of monocytes in preterm sheep

Boris Kramer, Machiko Ikegami, Timothy James Murugesan Moss, Ilias Nitsos, John Newnham, Alan Jobe

Research output: Contribution to journalArticleResearchpeer-review

Abstract

The preterm fetus is immune naive and has immature innate immune function. Although the preterm fetus is frequently exposed to chorioamnionitis, the effects of exposure of the fetal lung to inflammation on innate immune responses are unknown. Using the fetal sheep model of chorioamnionitis, cord blood monocytes were isolated from preterm lambs 1 to 14 days after intra-amniotic endotoxin injection, cultured for approximately 16 hours, and challenged with endotoxin in vitro. Compared with monocytes from adult sheep, the preterm monocytes produced less H(2)O(2) and interleukin-6, and toll-like receptor 4 expression was decreased. Three days after intra-amniotic endotoxin exposure, preterm monocyte responses to in vitro endotoxin challenge demonstrated decreased H(2)O(2) and interleukin-6 production and decreased CD14 and major histocompatibility complex class II expression. Preterm monocyte responses 7 to 14 days after endotoxin tended to exceed those of adults and preterm control animals indicating augmented function. In contrast, a second intra-amniotic endotoxin injection 7 days after the initial endotoxin exposure suppressed monocyte function at 14 days. The fetal monocytes demonstrated patterns of responses consistent with endotoxin tolerance (immune paralysis) as well as maturation of function. Modulation of fetal innate immune responses by exposure to inflammation may alter subsequent immune adaptation after birth.
Original languageEnglish
Pages (from-to)73 - 77
Number of pages5
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume171
Issue number1
DOIs
Publication statusPublished - 2005
Externally publishedYes

Cite this

Kramer, Boris ; Ikegami, Machiko ; Moss, Timothy James Murugesan ; Nitsos, Ilias ; Newnham, John ; Jobe, Alan. / Endotoxin-induced chorioamnionitis modulates innate immunity of monocytes in preterm sheep. In: American Journal of Respiratory and Critical Care Medicine. 2005 ; Vol. 171, No. 1. pp. 73 - 77.
@article{8ff0d303ec694865ab0fecfe0369ccc8,
title = "Endotoxin-induced chorioamnionitis modulates innate immunity of monocytes in preterm sheep",
abstract = "The preterm fetus is immune naive and has immature innate immune function. Although the preterm fetus is frequently exposed to chorioamnionitis, the effects of exposure of the fetal lung to inflammation on innate immune responses are unknown. Using the fetal sheep model of chorioamnionitis, cord blood monocytes were isolated from preterm lambs 1 to 14 days after intra-amniotic endotoxin injection, cultured for approximately 16 hours, and challenged with endotoxin in vitro. Compared with monocytes from adult sheep, the preterm monocytes produced less H(2)O(2) and interleukin-6, and toll-like receptor 4 expression was decreased. Three days after intra-amniotic endotoxin exposure, preterm monocyte responses to in vitro endotoxin challenge demonstrated decreased H(2)O(2) and interleukin-6 production and decreased CD14 and major histocompatibility complex class II expression. Preterm monocyte responses 7 to 14 days after endotoxin tended to exceed those of adults and preterm control animals indicating augmented function. In contrast, a second intra-amniotic endotoxin injection 7 days after the initial endotoxin exposure suppressed monocyte function at 14 days. The fetal monocytes demonstrated patterns of responses consistent with endotoxin tolerance (immune paralysis) as well as maturation of function. Modulation of fetal innate immune responses by exposure to inflammation may alter subsequent immune adaptation after birth.",
author = "Boris Kramer and Machiko Ikegami and Moss, {Timothy James Murugesan} and Ilias Nitsos and John Newnham and Alan Jobe",
year = "2005",
doi = "10.1164/rccm.200406-745OC",
language = "English",
volume = "171",
pages = "73 -- 77",
journal = "American Journal of Respiratory and Critical Care Medicine",
issn = "1073-449X",
publisher = "American Thoracic Society",
number = "1",

}

Endotoxin-induced chorioamnionitis modulates innate immunity of monocytes in preterm sheep. / Kramer, Boris; Ikegami, Machiko; Moss, Timothy James Murugesan; Nitsos, Ilias; Newnham, John; Jobe, Alan.

In: American Journal of Respiratory and Critical Care Medicine, Vol. 171, No. 1, 2005, p. 73 - 77.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Endotoxin-induced chorioamnionitis modulates innate immunity of monocytes in preterm sheep

AU - Kramer, Boris

AU - Ikegami, Machiko

AU - Moss, Timothy James Murugesan

AU - Nitsos, Ilias

AU - Newnham, John

AU - Jobe, Alan

PY - 2005

Y1 - 2005

N2 - The preterm fetus is immune naive and has immature innate immune function. Although the preterm fetus is frequently exposed to chorioamnionitis, the effects of exposure of the fetal lung to inflammation on innate immune responses are unknown. Using the fetal sheep model of chorioamnionitis, cord blood monocytes were isolated from preterm lambs 1 to 14 days after intra-amniotic endotoxin injection, cultured for approximately 16 hours, and challenged with endotoxin in vitro. Compared with monocytes from adult sheep, the preterm monocytes produced less H(2)O(2) and interleukin-6, and toll-like receptor 4 expression was decreased. Three days after intra-amniotic endotoxin exposure, preterm monocyte responses to in vitro endotoxin challenge demonstrated decreased H(2)O(2) and interleukin-6 production and decreased CD14 and major histocompatibility complex class II expression. Preterm monocyte responses 7 to 14 days after endotoxin tended to exceed those of adults and preterm control animals indicating augmented function. In contrast, a second intra-amniotic endotoxin injection 7 days after the initial endotoxin exposure suppressed monocyte function at 14 days. The fetal monocytes demonstrated patterns of responses consistent with endotoxin tolerance (immune paralysis) as well as maturation of function. Modulation of fetal innate immune responses by exposure to inflammation may alter subsequent immune adaptation after birth.

AB - The preterm fetus is immune naive and has immature innate immune function. Although the preterm fetus is frequently exposed to chorioamnionitis, the effects of exposure of the fetal lung to inflammation on innate immune responses are unknown. Using the fetal sheep model of chorioamnionitis, cord blood monocytes were isolated from preterm lambs 1 to 14 days after intra-amniotic endotoxin injection, cultured for approximately 16 hours, and challenged with endotoxin in vitro. Compared with monocytes from adult sheep, the preterm monocytes produced less H(2)O(2) and interleukin-6, and toll-like receptor 4 expression was decreased. Three days after intra-amniotic endotoxin exposure, preterm monocyte responses to in vitro endotoxin challenge demonstrated decreased H(2)O(2) and interleukin-6 production and decreased CD14 and major histocompatibility complex class II expression. Preterm monocyte responses 7 to 14 days after endotoxin tended to exceed those of adults and preterm control animals indicating augmented function. In contrast, a second intra-amniotic endotoxin injection 7 days after the initial endotoxin exposure suppressed monocyte function at 14 days. The fetal monocytes demonstrated patterns of responses consistent with endotoxin tolerance (immune paralysis) as well as maturation of function. Modulation of fetal innate immune responses by exposure to inflammation may alter subsequent immune adaptation after birth.

UR - http://ajrccm.atsjournals.org/cgi/reprint/171/1/73

U2 - 10.1164/rccm.200406-745OC

DO - 10.1164/rccm.200406-745OC

M3 - Article

VL - 171

SP - 73

EP - 77

JO - American Journal of Respiratory and Critical Care Medicine

JF - American Journal of Respiratory and Critical Care Medicine

SN - 1073-449X

IS - 1

ER -