Infection and labor. IV. Cachectin-tumor necrosis factor in the amniotic fluid of women with intraamniotic infection and preterm labor

Roberto Romero*, Kirk R. Manogue, Murray D. Mitchell, Ying King Wu, Enrique Oyarzun, John C. Hobbins, Anthony Cerami

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

384 Scopus citations

Abstract

A growing body of evidence supports a causal link between subclinical intrauterine infection and preterm labor. The mechanisms responsible for the onset of parturition in this setting have not been elucidated. The conventional view has been that bacterial products increase prostaglandin biosynthesis by intrauterine tissues and this, in turn, leads to the onset of labor. An alternative or complementary mechanism is that microbial products activate the host monocyte-macrophage system and that cytokines released during this process signal the initiation of parturition by stimulating prostaglandin biosynthesis by intrauterine tissues. This study was conducted to determine if cachectin-tumor necrosis factor is present in the amniotic fluid of women with intraamniotic infection and whether this cytokine can alter the rate of prostaglandin biosynthesis by intrauterine tissues. Amniotic fluid from 54 women was assayed for tumor necrosis factor. Tumor necrosis factor was not detectable in the amniotic fluid of women without intraamniotic infection regardless of the presence or absence of term or preterm labor. On the other hand, the amniotic fluid of 11 of 15 women with preterm labor and intraamniotic infection had measurable tumor necrosis factor. This cytokine stimulated prostaglandin E2 biosynthesis by amnion cells in monolayer culture in a dose-dependent fashion. These data support the concept that macrophage activation is involved in the onset of human parturition in the setting of infection. We propose that the host (fetus and/or mother) signals the onset of parturition through the secretion of inflammatory cytokines released in response to bacterial invasion.

Original languageEnglish
Pages (from-to)336-341
Number of pages6
JournalAmerican Journal of Obstetrics and Gynecology
Volume161
Issue number2
DOIs
StatePublished - Aug 1989
Externally publishedYes

Keywords

  • Tumor necrosis factor
  • cytokines
  • interleukin-1
  • intraamniotic infection
  • labor
  • parturition
  • prematurity
  • preterm labor
  • prostaglandins

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