Intra-amniotic endotoxin: chorioamnionitis precedes lung maturation in preterm lambs

Kallapur, Suhas G.; Willet, Karen E.; Jobe, Alan H.; Ikegami, Machiko; Bachurski, Cindy J.

doi:10.1152/ajplung.2001.280.3.l527

Cited by 192 publications

(287 citation statements)

References 51 publications

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“…This is consistent with our previous findings at 125 d GA regarding treatment after one or two doses of LPS (4,20,21). Our findings show that the increase in neutrophils at 133 d was evidence of a persistent response to the initial inflammatory stimulus.…”

Section: Discussionsupporting

confidence: 93%

Effects of intra-amniotic lipopolysaccharide exposure on the fetal lamb lung as gestation advances

et al. 2014

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Background: Intra-amniotic lipopolysaccharide (LPS) exposure may affect neonatal outcome by altering fetal lung and immune system development. We hypothesized that intra-amniotic LPS exposure would cause persistent fetal pulmonary responses as the lungs develop in utero. Methods: Fetal lambs were exposed to intra-amniotic LPS at 118 or at 118 and 123 d of gestational age (GA) with delivery at 125, 133, or 140 d (term = 147 d). Immune responses, PU.1 expression, toll-like receptor (tLR)-1,2,4,6 mRNA levels, mast cell levels, and pulmonary elastin deposition were evaluated. results: After a single dose of LPS, pulmonary inflammatory responses were observed with increases of (i) PU.1 and tLR1 at 125 d GA and (ii) monocytes, lymphocytes, tLR2, and tLR6 at 133 d GA. Repetitive LPS exposure resulted in (i) increases of neutrophils, monocytes, PU.1, and tLR1 at 125 d GA; (ii) increases of neutrophils, PU.1, and tLR2 at 133 d GA; and (iii) decreases of mast cells, elastin foci, tLR4, and tLR6 at early gestation. At 140 d GA, only PU.1 was increased after repetitive LPS exposure. conclusion: The preterm fetal lung can respond to a single exposure or repeated exposures from intra-amniotic LPS in multiple ways, but the absence of inflammatory and structural changes in LPS-exposed fetuses delivered near term suggest that the fetus can resolve an inflammatory stimulus in utero with time.

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Section: Discussionsupporting

confidence: 93%

Effects of intra-amniotic lipopolysaccharide exposure on the fetal lamb lung as gestation advances

et al. 2014

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“…Chorioamnionitis mediated by intra-amniotic LPS induces unique fetal lung and systemic inflammatory responses (7,8). The normal fetus has intermittent respirations with occasional gasping.…”

Section: Discussionmentioning

confidence: 99%

“…We developed a preterm lamb model of chorioamnionitis in which intra-amniotic LPS directly contacts the fetal lung and causes inflammatory cell influx and expression of proinflammatory cytokines in the fetal lung (7)(8)(9). We also reported that structural changes resembling bronchopulmonary dysplasia (fewer alveoli, vascular injury responses) occur in the preterm fetal lung after exposure to a single injection of intra-amniotic LPS (10,11).…”

Section: Pulmonary and Systemic Endotoxin Tolerance In Pretermmentioning

confidence: 99%

Pulmonary and Systemic Endotoxin Tolerance in Preterm Fetal Sheep Exposed to Chorioamnionitis

Kallapur

Jobe

Ball

et al. 2007

The Journal of Immunology

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110

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In a model of human chorioamnionitis, fetal sheep exposed to a single injection, but not repeated injections, of intra-amniotic endotoxin develop lung injury responses. We hypothesized that repeated exposure to intra-amniotic endotoxin induces endotoxin tolerance. Fetal sheep were given intra-amniotic injections of saline (control) or Escherichia coli LPS O55:B5 (10 mg) either 2 days (2-day group, single exposure), 7 days (7-day group, single exposure), or 2 plus 7 days (2- and 7-day repeat exposure) before preterm delivery at 124 days gestation (term = 150 days). Endotoxin responses were assessed in vivo in the lung and liver, and in vitro in monocytes from the blood and the lung. Compared with the single 2-day LPS exposure group, the (2 plus 7 days) repeat LPS-exposed lambs had: 1) decreased lung neutrophil and monocyte inducible NO synthase (NOSII) expression, and 2) decreased lung cytokine and liver serum amyloid A3 mRNA expression. In the lung, serum amyloid A3 mRNA expression decreased in the airway epithelial cells but not in the lung inflammatory cells. Unlike the single 7-day LPS exposure group, peripheral blood and lung monocytes from the repeat-LPS group did not increase IL-6 secretion or hydrogen peroxide production in response to in vitro LPS. Compared with controls, TLR4 expression did not change but IL-1R-associated kinase M expression increased in the monocytes from repeat LPS-exposed lambs. These results are consistent with the novel finding of endotoxin tolerance in preterm fetal lungs exposed to intra-amniotic LPS. The findings have implications for preterm infants exposed to chorioamnionitis for both responses to lung injury and postnatal nosocomial infections.

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“…51 Proinflammatory cytokine mRNA in the fetal liver was inconsistently and minimally increased; plasma IL-6 and IL-8 levels were minimally increased. 33,49,52 Also, cytokine mRNA levels in the placenta and gut did not increase appreciably. 49 Therefore, a diffuse systemic fetal inflammatory response did not explain the local lung inflammation.…”

Section: How Endotoxin Signals Lung Maturationmentioning

confidence: 91%

“…33,49,50 Diffuse inflammation of the chorioamnion could release effector molecules into the fetal systemic circulation and indirectly induce lung inflammation and maturation. However, intra-amniotic endotoxin had very modest effects on circulating white blood cells and platelets 33,45 and did not adversely affect fetal well-being.…”

Section: How Endotoxin Signals Lung Maturationmentioning

confidence: 99%

Antenatal inflammation and lung injury: prenatal origin of neonatal disease

Kramer¹

2008

J Perinatol

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Intra-amniotic endotoxin: chorioamnionitis precedes lung maturation in preterm lambs

Cited by 192 publications

References 51 publications

Effects of intra-amniotic lipopolysaccharide exposure on the fetal lamb lung as gestation advances

Effects of intra-amniotic lipopolysaccharide exposure on the fetal lamb lung as gestation advances

Pulmonary and Systemic Endotoxin Tolerance in Preterm Fetal Sheep Exposed to Chorioamnionitis

Antenatal inflammation and lung injury: prenatal origin of neonatal disease

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