THE NATURAL INTERLEUKIN-1 RECEPTOR ANTAGONIST IN THE FETAL, MATERNAL, AND AMNIOTIC-FLUID COMPARTMENTS - THE EFFECT OF GESTATIONAL-AGE, FETAL GENDER, AND INTRAUTERINE INFECTION
THE NATURAL INTERLEUKIN-1 RECEPTOR ANTAGONIST IN THE FETAL, MATERNAL, AND AMNIOTIC-FLUID COMPARTMENTS - THE EFFECT OF GESTATIONAL-AGE, FETAL GENDER, AND INTRAUTERINE INFECTION
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DOI：
10.1016/s0002-9378(94)70058-3
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发表时间：
1994-10-01
影响因子：
9.8
通讯作者：
COTTON, DB
中科院分区：
文献类型：
--
作者：
ROMERO, R;GOMEZ, R;COTTON, DB
目的：白细胞介素-1受体拮抗剂是一种新发现的细胞因子，可在体内外阻断白细胞介素-1的生物学效应。这种细胞因子是羊水的生理成分，被认为在细胞因子网络的稳态中至关重要。本研究旨在系统地检测白细胞介素-1受体拮抗剂在有和无微生物侵入羊膜腔的妇女中，在足月分娩和早产期间在母体、胎儿和羊水室中的生物利用度。患者人群包括（1）妊娠中期的孕妇（n = 42），（2）因诊断目的而接受脐带穿刺术的患者（n = 39），（3）早产患者（n = 126），（4）足月妊娠妇女（n = 102），和（5）健康非妊娠妇女（n = 8）。培养羊水中的需氧菌和厌氧菌，以及支原体。通过酶联免疫测定法测定母体和胎儿血浆、羊水和新生儿尿液中的白细胞介素-1受体拮抗剂浓度。结果：（1）脐带穿刺胎儿血浆中IL-1受体拮抗剂含量正常，且随孕周增加而增加（n = 39; r = 0.61，p < 0.001）; (2)足月非临产患者的羊水白细胞介素1受体拮抗剂浓度高于中期妊娠患者（中位数40.1 ng/ml，范围5.7至213.1 vs中位数16.2 ng/ml，范围3.2至62.2，分别为p < 0.001）。(3)羊水和脐带血浆白细胞介素1受体拮抗剂浓度在有早产和羊膜腔微生物侵袭的患者中显著高于那些没有羊膜腔微生物侵袭的患者（羊水：中位数219.9 ng/ml，范围35.4 - 504 vs中位数80.6 ng/ml，范围24.3 - 399，p < 0.001;脐带血浆：中值4.8ng/ml，范围0.3至167.0对中值1.0ng/ml，范围0至276.0，p < 0.05）。相反，这些差异在足月分娩的患者中没有发现，无论是否有微生物侵入羊膜腔。(4)足月和早产儿羊水和新生儿尿中白细胞介素1受体拮抗剂的浓度，女性胎儿均显著高于男性胎儿（羊水，早产：中位数191.9 ng/ml，范围51.6 - 504.0 vs中位数61.1 ng/ml，范围11.5 - 284.9，分别为p < 0.001;羊水，足月：中位数58.7 ng/ml，范围25.5 - 264.0 vs中位数33.9 ng/ml，范围3.4 - 132.4，分别为p < 0.001;新生儿尿液：中位数317 ng/ml，范围59.0 - 440.8 vs中位数12.2 ng/ml，范围2.5 - 61.6，分别为p < 0.005）。（1）白细胞介素-1受体拮抗剂在生理上存在于胎儿、母体和羊水隔室中;（2）早产时羊膜腔的微生物侵入与该细胞因子在胎儿和羊水隔室中而不是在母体血浆中的浓度显著增加相关;（3）胎儿尿是羊水白细胞介素-1受体拮抗剂的来源;（4）胎儿血浆IL-1受体拮抗剂浓度随孕周增加而升高;（5）胎儿性别对羊水及新生儿尿液中IL-1受体拮抗剂浓度有显著影响。
OBJECTIVES: The interleukin-1 receptor antagonist is a newly discovered cytokine that blocks the biologic effects of interleukin-1 in vitro and in vivo. This cytokine is a physiologic component of amniotic fluid and is considered to be of critical importance in the homeostasis of the cytokine network. This study was undertaken to systematically examine the bioavailability of interleukin-1 receptor antagonist in the maternal, fetal, and amniotic fluid compartments during term and preterm parturition in women with and without microbial invasion of the amniotic cavity.STUDY DESIGN: The patient population consisted of (1) pregnant women in the midtrimester (n = 42), (2) patients who underwent cordocentesis for diagnostic purposes (n = 39), (3) patients with preterm labor (n = 126), (4) women with term gestation (n = 102), and (5) healthy nonpregnant women (n = 8). Amniotic fluid was cultured for aerobic and anaerobic bacteria, as well as Mycoplasma sp. Interleukin-1 receptor antagonist concentrations were determined by enzyme-linked immunoassay in maternal and fetal plasma, amniotic fluid, and neonatal urine. Microbial invasion of the amniotic cavity was defined as the presence of a positive amniotic fluid culture for microorganisms.RESULTS: (1) Interleukin-1 receptor antagonist was normally present in fetal plasma samples obtained by cordocentesis, and its concentration increased with advancing gestational age (n = 39; r = 0.61, p < 0.001). (2) Patients at term not in labor had higher amniotic fluid interleukin-1 receptor antagonist concentrations than patients in the midtrimester (median 40.1 ng/ml, range 5.7 to 213.1 vs median 16.2 ng/ml, range 3.2 to 62.2, respectively, p < 0.001). (3) Amniotic fluid and cord plasma interleukin-1 receptor antagonist concentrations were significantly higher in patients with preterm labor and microbial invasion of the amniotic cavity than in those without microbial invasion of the amniotic cavity (amniotic fluid: median 219.9 ng/ml, range 35.4 to 504 vs median 80.6 ng/ml, range 24.3 to 399, respectively, p < 0.001; umbilical cord plasma: median 4.8 ng/ml, range 0.3 to 167.0 vs median 1.0 ng/ml, range 0 to 276.0, respectively, p < 0.05). In contrast, these differences were not found in patients with term labor either with or without microbial invasion of the amniotic cavity. (4) In both term and preterm patients the amniotic fluid and neonatal urine concentrations of interleukin-1 receptor antagonist were significantly higher in female fetuses than in male fetuses (amniotic fluid, preterm: median 191.9 ng/ml, range 51.6 to 504.0 vs median 61.1 ng/ml, range 11.5 to 284.9, respectively, p < 0.001; amniotic fluid, term: median 58.7 ng/ml, range 25.5 to 264.0 vs median 33.9 ng/ml, range 3.4 to 132.4, respectively, p < 0.001; neonatal urine: median 317 ng/ml, range 59.0 to 440.8 vs median 12.2 ng/ml, range 2.5 to 61.6, respectively, p < 0.005).CONCLUSIONS: (1) Interleukin-1 receptor antagonist is physiologically present in the fetal, maternal, and amniotic fluid compartments; (2) microbial invasion of the amniotic cavity in the preterm gestation is associated with a significant increase in the concentrations of this cytokine in the fetal and amniotic fluid compartments but not in maternal plasma; (3) fetal urine is a source of amniotic fluid interleukin-1 receptor antagonist; (4) fetal plasma interleukin-1 receptor antagonist concentrations increase with gestational age; (5) there is a significant effect of fetal gender in amniotic fluid and neonatal urine concentrations of interleukin-1 receptor antagonist.