The natural interleukin-1 receptor antagonist in tem and preterm parturition

Roberto Romero, Waldo Sepulveda, Moshe Mazor, Francisco Brandt, David B. Cotton, Charles A. Dinarello, Murray D. Mitchell

Research output: Contribution to journalArticlepeer-review

118 Scopus citations

Abstract

OBJECTIVE: interleukin-1 has been implicated in the mechanisms responsible for preterm labor in the setting of infection. The interleukin-1 receptor antagonist is a new member of the interleukin-1 gene family that inhibits the biologic effects of interleukin-1 by blocking its receptors. Reduction of interleukin-1-induced prostaglandin production by intrauterine tissues may have potential value in the treatment of preterm labor associated with infection. The purpose of these studies was (1) to determine interleukin-1 receptor antagonist levels in the amniotic fluid of women with term and preterm labor (with and without infection) and (2) to study the effects of interleukin-1 receptor antagonist on interleukin-1-induced prostaglandin biosynthesis by human amnion and chorion. STUDY DESIGN: Amniotic fluid was obtained from women in the midtrimester of pregnancy (n = 20), atterm pregnancy (with and without labor, n = 69), and in preterm labor (n = 47). Fluid was cultured for aerobic and anaerobic bacteria and Mycoplasmas. interleukin-1α, interleukin-1β, and interleukin-1 receptor antagonist concentrations were measured by immunoassays previously validated for human amniotic fluid. The effect of interleukin-1 receptor antagonist on interleukin-1-induced prostaglandin production by amnion and chorion was studied with primary cultures. Cells were incubated with interleukin-1 receptor antagonist and interleukin-1α or interleukin-1β for 16 hours. Prostaglandin E2 released into the media was assayed by immunoassay. RESULTS: (1) interleukin-1 receptor antagonist was present in all amniotic fluid samples; (2) amniotic fluid contains the highest interleukin-1 receptor antagonist concentrations detected in any biologic fluid to date; (3) amniotic fluid interleukin-1 receptor antagonist concentrations were not increased in women with preterm labor and intraamniotic infection in spite of dramatically elevated concentrations of interleukin-1∝ and interleukin-1β in the same fluid (median 22 ng/ml and range 0.16 to 70 for preterm labor with negative amniotic fluid culture vs median 30 ng/ml and range 6 to 70 for preterm labor with positive amniotic fluid culture; p > 0.05); (4) interleukin-1 receptor antagonist reduced interleukin-1β-induced prostaglandin E2 production by amnion and chorion in a dose-dependent manner; (5) interleukin-1 receptor antagonist by itself did not stimulate prostaglandin E2 release by amnion and chorion when used in concentrations ranging from 0.1 to 1000 ng/ml. CONCLUSIONS: (1) interleukin-1 receptor antagonist is a physiologic component of amniotic fluid; (2) therelease of interleukin-1α and interleukin-1β into the amniotic fluid in women with preterm labor is not associated with an increase in interleukin-1 receptor antagonist levels in amniotic fluid; (3) interleukin-1 receptor antagonist reduces interleukin-1-induced prostaglandin production by amnion and chorion; (4) exogenous anticytokine agents may be of value in the treatment of preterm labor. (Am J Obstet Gynecol 1992;167:863–72.)

Original languageEnglish
Pages (from-to)863-872
Number of pages10
JournalAmerican Journal of Obstetrics and Gynecology
Volume167
Issue number4
DOIs
StatePublished - 1 Jan 1992
Externally publishedYes

Keywords

  • Interleukin-1 receptor antagonist
  • amniotic fluid
  • intraamnioticinfection
  • preterm labor

ASJC Scopus subject areas

  • Obstetrics and Gynecology

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