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Transforming growth factor-β2 prevents preterm delivery induced by interleukin-α and tumor necrosis factor-α the rabbit

Authors
  • Bry, Kristina
  • Hallman, Mikko
Type
Published Article
Journal
American Journal of Obstetrics and Gynecology
Publisher
Elsevier
Publication Date
Jan 01, 1993
Accepted Date
Oct 31, 1992
Volume
168
Issue
4
Pages
1318–1322
Identifiers
DOI: 10.1016/0002-9378(93)90388-Y
Source
Elsevier
Keywords
License
Unknown

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-α and tumor necrosis factor-β2, and whether transforming growth factor-p2, 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-α (150 µg) and tumor necrosis factor-α (1.25 µg), 50 ng of transforming growth factor-β2 concomitantly with interleukin-α and tumor necrosis factor-α, 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-β2 (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 F2α. were measured in the amniotic fluid on day 27 of gestation. The statistics used were Fisher's exact test, the X2 test, and the Mann-Whitney U test.Results: Altogether 61 of 191 fetuses (32%) were born prematurely in the interleukin-1 α-tumor necrosis factor-a 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-1a tumor necrosis factor-α-transforming growth factor-β2 group and in the control group, respectively. Of the 23 animals injected with interleukin-1 α and tumor necrosis factor-α, 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-α group were born prematurely. The prostaglandin E2 concentrations in the amniotic fluids were higher in the interleukin-1a-tumor necrosis factor-α group than in the interleukin-lα-tumor necrosis factor-α-transforming growth factor-β2 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-la and tumor necrosis factor-a. Transforming growth factor-P2 prevents the cytokine-induced increase in premature delivery.

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