Cachectin/tumor necrosis factor-α formation in human decidua. Potential role of cytokines in infection-induced preterm labor

M. L. Casey, S. M. Cox, B. Beutler, L. Milewich, P. C. MacDonald

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294 Scopus citations

Abstract

This study was conducted as part of an investigation to evaluate the hypothesis that bacterial toxins (LPS or lipoteichoic acid), acting on macrophage-like uterine decidua to cause increased formation of cytokines, may be involved in the pathogenesis of infection-associated preterm labor. We found that cachectin/tumor necrosis factor-α (TNF-α) was synthesized and secreted into the culture medium by human decidual cells and explants in response to treatment with LPS. LPS treatment also caused an increase in PGF(2α) production by decidual cells and explants. In amnion cells in monolayer culture, TNF-α stimulated PGE2 formation, and TNF-α was cytostatic (inhibited [3H]thymidine incorporation into DNA) but not cytolytic in amnion cells. TNF-α was not detectable (<0.34 ng/ml) in the amniotic fluid of normal pregnancies at midtrimester or at term before or after the onset of labor (n = 44); but TNF-α was present at concentrations between 2.8 and 22.3 ng/ml in amniotic fluids of 4 of 20 pregnancies with intact membranes complicated by preterm labor (<34 wk gestational age). LPS was present in 10 of the 20 amniotic fluids of preterm labor pregnancies, including all four in which TNF-α was present. Bacteria were identified in only one of the four LPS-positive, TNF-α-positive fluids. Cytokine formation in macrophage-like decidua may serve a fundamental role in the pathogenesis of preterm labor, including increased prostaglandin formation and premature rupture of the membranes.

Original languageEnglish (US)
Pages (from-to)430-436
Number of pages7
JournalJournal of Clinical Investigation
Volume83
Issue number2
DOIs
StatePublished - 1989

ASJC Scopus subject areas

  • General Medicine

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