转化生长因子-β2可预防白细胞介素-1α和肿瘤坏死因子-α诱导的兔早产。

Transforming growth factor-beta 2 prevents preterm delivery induced by interleukin-1 alpha and tumor necrosis factor-alpha in the rabbit.

作者信息

Bry K, Hallman M

机构信息

Department of Pediatrics, University of California, Irvine 92717.

出版信息

Am J Obstet Gynecol. 1993 Apr;168(4):1318-22. doi: 10.1016/0002-9378(93)90388-y.

DOI:10.1016/0002-9378(93)90388-y

PMID:8475982

Abstract

OBJECTIVES

The purpose of the study was to determine whether preterm parturition in the rabbit can be induced by intraamniotic injection of proinflammatory cytokines, interleukin-1 alpha and tumor necrosis factor-alpha, and whether transforming growth factor-beta 2, an inhibitor of the cytokine-induced prostaglandin synthesis, modifies the effect of these cytokines.

STUDY DESIGN

New Zealand White rabbits were injected in each amniotic cavity on day 24 of gestation with one of the following: a combination of interleukin-1 alpha (150 ng) and tumor necrosis factor-alpha (1.25 micrograms), 50 ng of transforming growth factor-beta 2 concomitantly with interleukin-1 alpha and tumor necrosis factor-alpha, or vehicle. In the first study the animals were observed for signs of delivery until day 29 of gestation. In the second study the effect of transforming growth factor-beta 2 (50 ng/fetus) on the rate of premature delivery was evaluated. In the third study the concentrations of prostaglandin E2 and 13,14-dihydro-15-keto-prostaglandin F2 alpha were measured in the amniotic fluid on day 27 of gestation. The statistics used were Fisher's exact test, the chi 2 test, and the Mann-Whitney U test.

RESULTS

Altogether 61 of 191 fetuses (32%) were born prematurely in the interleukin-1 alpha-tumor necrosis factor-alpha group, whereas only two of 161 fetuses (1.2%) (p = 0.0001) and one of 159 (0.6%) (p = 0.0001) were born prematurely in the interleukin-1 alpha-tumor necrosis factor-alpha-transforming growth factor-beta 2 group and in the control group, respectively. Of the 23 animals injected with interleukin-1 alpha and tumor necrosis factor-alpha, six (26%) delivered all of their fetuses prematurely versus none in the other groups (p = 0.02). None of the 88 fetuses in the transforming growth factor-beta 2 group were born prematurely. The prostaglandin E2 concentrations in the amniotic fluids were higher in the interleukin-1 alpha-tumor necrosis factor-alpha group than in the interleukin-1 alpha-tumor necrosis factor-alpha-transforming growth factor-beta 2 group (p = 0.05) or in the control group (p = 0.02).

CONCLUSIONS

Preterm parturition can be provoked in the rabbit by intraamniotic injections of interleukin-1 alpha and tumor necrosis factor-alpha. Transforming growth factor-beta 2 prevents the cytokine-induced increase in premature delivery.

摘要

目的

本研究旨在确定羊膜腔内注射促炎细胞因子白细胞介素 -1α 和肿瘤坏死因子 -α 是否能诱发兔早产，以及细胞因子诱导的前列腺素合成抑制剂转化生长因子 -β2 是否能改变这些细胞因子的作用。

研究设计

在妊娠第24天，向新西兰白兔的每个羊膜腔内注射以下物质之一：白细胞介素 -1α（150 ng）和肿瘤坏死因子 -α（1.25微克）的组合、50 ng转化生长因子 -β2 与白细胞介素 -1α 和肿瘤坏死因子 -α 同时注射，或注射赋形剂。在第一项研究中，观察动物直至妊娠第29天的分娩迹象。在第二项研究中，评估转化生长因子 -β2（50 ng/胎儿）对早产率的影响。在第三项研究中，于妊娠第27天测量羊水中前列腺素E2和13,14 - 二氢 -15 - 酮 - 前列腺素F2α 的浓度。所使用的统计方法为Fisher精确检验、卡方检验和Mann - Whitney U检验。

结果

在白细胞介素 -1α - 肿瘤坏死因子 -α 组中，191只胎儿中有61只（32%）早产，而在白细胞介素 -1α - 肿瘤坏死因子 -α - 转化生长因子 -β2 组和对照组中，161只胎儿中分别仅有2只（1.2%）（p = 0.0001）和159只中的1只（0.6%）（p = 0.0001）早产。在注射白细胞介素 -1α 和肿瘤坏死因子 -α 的23只动物中，有6只（26%）使其所有胎儿早产，而其他组均无此情况（p = 0.02）。转化生长因子 -β2 组的88只胎儿均未早产。白细胞介素 -1α - 肿瘤坏死因子 -α 组羊水中的前列腺素E2浓度高于白细胞介素 -1α - 肿瘤坏死因子 -α - 转化生长因子 -β2 组（p = 0.05）或对照组（p = 0.02）。