Document Detail

Macrophage migration inhibitory factor in patients with preterm parturition and microbial invasion of the amniotic cavity.
MedLine Citation:
PMID:  16390807     Owner:  NLM     Status:  MEDLINE    
OBJECTIVE: Macrophage migration inhibitory factor (MIF) has emerged as an important mediator of septic shock. The administration of MIF increases lethality during endotoxemia, whereas neutralization of this cytokine prevents endotoxic shock and death associated with bacterial infection. The objective of this study was to determine whether there is a change in the amniotic fluid concentration of MIF in intra-amniotic infection and human parturition.
STUDY DESIGN: A cross-sectional study was conducted in women in the following categories: (1) mid-trimester (n = 84); (2) preterm labor and intact membranes who delivered at term (n = 33), who delivered preterm (n = 53) and preterm labor with intra-amniotic infection (n = 23); (3) preterm premature rupture of membranes (PROM) with (n = 25) and without intra-amniotic infection (n = 26); and (4) term with intact membranes, in labor (n = 52) and not in labor (n = 31). MIF concentrations in amniotic fluid were determined using a sensitive and specific immunoassay. MIF concentrations in maternal plasma were also determined in patients with preterm labor and intact membranes. Immunohistochemistry was conducted in chorioamniotic membranes obtained from a different set of patients presenting with preterm labor with (n = 18) and without (n = 20) histologic chorioamnionitis. Quantitative reverse transcription-polymerase chain reaction (RT-PCR) was used to measure MIF mRNA expression in chorioamniotic membranes of patients with preterm labor with (n = 13) and without (n = 13) histologic chorioamnionitis. Parametric and non-parametric, receiver-operating characteristic (ROC) curve, survival analysis, and Cox regression model were used for analysis.
RESULTS: Immunoreactive MIF was detectable in 96% (313/327) of amniotic fluid samples. The concentration of amniotic fluid MIF at term was higher than that in the mid-trimester (p = 0.004). Intra-amniotic infection in women with preterm labor and preterm PROM was associated with a significant increase in median amniotic fluid MIF concentration (p < 0.001 and 0.004, respectively). Patients with preterm labor with sterile amniotic fluid who delivered preterm had a significantly higher median amniotic fluid MIF concentration than those who delivered at term (p = 0.007). Among patients with preterm labor with intact membranes, survival analysis indicated that the median amniocentesis-to-delivery interval was significantly shorter in patients whose amniotic fluid concentrations of MIF were above 302 ng/ml than those below this cutoff value (p < 0.001). Human parturition at term was not associated with changes in the amniotic fluid MIF concentrations (p > 0.05). There was no significant difference in median maternal plasma MIF concentrations among patients with preterm labor and intact membranes who delivered at term, those who delivered preterm, and those who had intra-amniotic infection (p > 0.05 for all comparisons). Immunohistochemistry demonstrated that MIF protein was present in amniotic epithelial cells, and the mean percentage of immunoreactive MIF-staining cells was higher in patients with histologic chorioamnionitis than in those without this lesion (p = 0.03). Similarly, the mean MIF mRNA expression was higher in chorioamniotic membranes obtained from patients with histologic chorioamnionitis than in those without this lesion (p = 0.03).
CONCLUSIONS: Intra-amniotic infection and preterm parturition, but not term parturition, are associated with a significant increase in amniotic fluid MIF concentrations. Among patients with preterm labor with intact membranes, elevated amniotic fluid concentrations of MIF are associated with intra-amniotic inflammation, histologic chorioamnionitis, and shorter amniocentesis-to-delivery interval. These changes in amniotic fluid were not reflected in maternal plasma. An increased expression of MIF protein and mRNA in chorioamniotic membranes was observed in patients with histologic choricamnionitis.
Tinnakorn Chaiworapongsa; Roberto Romero; Jimmy Espinoza; Yeon Mee Kim; Samuel Edwin; Emmanuel Bujold; Ricardo Gomez; Helena Kuivaniemi
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Intramural    
Journal Detail:
Title:  The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians     Volume:  18     ISSN:  1476-7058     ISO Abbreviation:  J. Matern. Fetal. Neonatal. Med.     Publication Date:  2005 Dec 
Date Detail:
Created Date:  2006-01-04     Completed Date:  2007-05-24     Revised Date:  2013-06-07    
Medline Journal Info:
Nlm Unique ID:  101136916     Medline TA:  J Matern Fetal Neonatal Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  405-16     Citation Subset:  IM    
Perinatology Research Branch, National Institute of Child Health and Human Development, NIH/DHHS, Bethesda, Maryland, USA.
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MeSH Terms
Amniotic Fluid / cytology,  metabolism*,  microbiology
Blood Proteins / metabolism
Case-Control Studies
Cross-Sectional Studies
Defensins / metabolism
Fetal Membranes, Premature Rupture / metabolism*
Gestational Age
Leukocyte Count
Macrophage Migration-Inhibitory Factors / physiology*
Macrophages / physiology
Obstetric Labor, Premature / metabolism*
Pregnancy Complications, Infectious / diagnosis,  metabolism*
Pregnancy Trimester, Second
Proportional Hazards Models
ROC Curve
Grant Support
Z01 HD002400-14/HD/NICHD NIH HHS
Reg. No./Substance:
0/Blood Proteins; 0/Defensins; 0/Macrophage Migration-Inhibitory Factors

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