THE NATURAL INTERLEUKIN-1 RECEPTOR ANTAGONIST IN TERM AND PRETERM PARTURITION

被引:120
作者
ROMERO, R
SEPULVEDA, W
MAZOR, M
BRANDT, F
COTTON, DB
DINARELLO, CA
MITCHELL, MD
机构
[1] TUFTS UNIV,SCH MED,DEPT MED,BOSTON,MA 02111
[2] YALE UNIV,SCH MED,DEPT OBSTET & GYNECOL,NEW HAVEN,CT 06510
[3] UNIV UTAH,MED CTR,DEPT OBSTET & GYNECOL,SALT LAKE CITY,UT 84112
[4] NICHHD,PERINATOL BRANCH,BETHESDA,MD 20892
关键词
INTERLEUKIN-1 RECEPTOR ANTAGONIST; PRETERM LABOR; AMNIOTIC FLUID; INTRAAMNIOTIC INFECTION;
D O I
10.1016/S0002-9378(12)80003-2
中图分类号
R71 [妇产科学];
学科分类号
100211 ;
摘要
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), at term pregnancy (with and without labor, n = 69), and in preterm labor (n = 47). Fluid was cultured for aerobic and anaerobic bacteria and Mycoplasmas. Interleukin-1alpha, interleukin-1beta, 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-1alpha or interleukin-1beta 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-1alpha and interleukin-1beta 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-1beta-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.
引用
收藏
页码:863 / 872
页数:10
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