Systemic fetal inflammation and reduced concentrations of macrophage migration inhibitory factor in tracheobronchial aspirate fluid of extremely premature infants.
ABSTRACT Macrophage migration inhibitory factor is a proinflammatory mediator of innate immunity, enhances cell growth, and plays a role in preterm delivery. We speculated that funisitis, reflecting fetal systemic inflammation, would be associated with higher concentrations of macrophage migration inhibitory factor in airways of extremely premature infants.
We measured macrophage migration inhibitory factor by enzyme linked immunosorbent assay in tracheobronchial aspirate fluid of 35 ventilated infants less than 30 weeks' gestational age, throughout the first week of life. Three groups were distinguished histologically: chorioamnionitis, funisitis, and control.
Unexpectedly, funisitis was associated with significantly decreased macrophage migration inhibitory factor in tracheobronchial aspirate fluid on day 1 (P < .01) and levels remained lower than in the chorioamnionitis group thereafter. For the 35 patients in total, macrophage migration inhibitory factor steadily declined.
Decreased macrophage migration inhibitory factor concentrations in airways of extremely premature infants with systemic fetal inflammation early in life might predispose them to pulmonary infection and interfere with maturation of the lung, contributing to adverse pulmonary outcome.
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ABSTRACT: Antenatal inflammation may be associated with adverse neonatal outcomes in several organ systems. Bacteria and a few viruses have been detected in cases of microbial invasion of the amniotic cavity which is referred to as chorioamnionitis. Many aspects of this disease remain unclear such as the causes, time of onset and the fetal responses. Chorioamnionitis was therefore induced in pregnant sheep by injections of lipopolysaccharide (LPS) or Ureaplasma species into the amniotic cavity under ultrasound guidance. LPS-induced chorioamnionitis caused a cascade of organ injury, inflammation, and remodeling. The organ-specific changes were accompanied by systemic effects. The systemic effects after LPS-induced chorioamnionitis resulted in immune suppression against several Toll-like receptor agonists (cross-tolerance). Ureaplasma induced chorioamnionitis made changes in the fetal lung structure depending on the time of infection during pregnancy. The mechanisms of inflammation, structural damage and decreased expression of growth factors need to be further studied to determine therapeutic targets in suitable animal models.Neonatology 01/2011; 99(4):320-5. · 2.57 Impact Factor
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ABSTRACT: An increasing body of evidence has revealed that interventions performed during resuscitation of extremely-low-gestational-age neonates (ELGANs) may have a direct influence on the immediate survival and also on long-term morbidity. It has been proposed that interventions in the delivery room and/or hypothermia could trigger changes constitutive of chronic lung disease. New approaches in the first minutes of life using more gentle parameters of intervention are being studied. Thus, titrating inspiratory fraction of oxygen, the use of non-invasive ventilation to reduce trauma to the lung, the use of polyethylene/polyurethane wrapping to avoid hypothermia and delaying cord clamping altogether constitute promising initiatives. The first minutes of life are a valuable window for intervention. However, whilst these practice changes make sense and there are emerging data to support them, further evidence including long-term follow up is needed to definitively change resuscitation procedures in ELGANs.Neonatology 01/2009; 95(4):286-98. · 2.57 Impact Factor
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ABSTRACT: BACKGROUND: The role and mechanism of action of MIF in bronchopulmonary dysplasia (BPD) are not known. We hypothesized that increased MIF signaling would ameliorate the pulmonary phenotype of BPD in the mouse lung. METHODS: We studied newborn wild type (WT), MIF knockout (MIFKO), and lung MIF transgenic (MIFTG) mice in room air and a BPD model, and examined the effects of administering a small molecule MIF agonist and antagonist. Lung morphometry was performed and mRNA and protein expression of vascular mediators were analyzed. RESULTS: The pulmonary phenotype of MIFKO and MIFTG mice lungs in room air (RA) and BPD model were comparable to the WT-BPD mice at postnatal (PN) day 14. Vascular endothelial growth factor (VEGF)-A, -R1 and Angiopoietin (Ang)1 mRNA were decreased, and Ang2 increased in the WT-BPD, MIFKO-RA, MIFKO-BPD, MIFTG-RA and MIFTG-BPD mice lungs, compared to appropriate controls. The protein expression of Ang1 in the MIFKO-RA was similar to WT-RA, but decreased in MIFTG-RA, and decreased in all the BPD groups. Ang2 was increased in MIFKO-RA, MIFTG-RA and in all 3 BPD groups. Tie2 was increased in WT-BPD compared to WT-RA, but decreased in MIFKO- and MIFTG- RA and BPD groups. VEGFR1 was uniformly decreased in MIFKO-RA, MIFTG-RA and in all 3 BPD groups. VEGF-A had a similar expression across all RA and BPD groups. There was partial recovery of the pulmonary phenotype in the WT-BPD model treated with the MIF agonist, and in the MIFTG mice treated with the MIF antagonist. CONCLUSIONS: These data point to the careful regulatory balance exerted by MIF in the developing lung and response to hyperoxia and support the potential therapeutic value of small molecule MIF modulation in BPD.Respiratory research 02/2013; 14(1):27. · 3.64 Impact Factor