Placental secretion of interleukin-1 and interleukin-1 receptor antagonist in preeclampsia: effect of magnesium sulfate

Abstract

Preeclampsia is a pregnancy-specific disorder characterized by hypertension and systemic endothelial dysfunction. Interleukin (IL)-1β is a possible mediator of maternal endothelial dysfunction in preeclampsia. Serum IL-1β as well as its natural inhibitor IL-1 receptor antagonist (IL-1Ra) were reported to be increased in women with preeclampsia. In the current study, we addressed the role of the placenta in controlling the circulatory levels of IL-1β and its natural inhibitor IL-1Ra in preeclampsia, and the possible effect of magnesium sulfate (MgSO(4)) on these levels. Using an ex vivo placental perfusion system, placentas from preeclamptic (n = 9) and normotensive (n = 6) pregnancies were perfused in presence or absence of MgSO(4). Perfusate samples were collected from the maternal and the fetal circulations of the perfusion system, and IL-1β and IL-1Ra were examined by enzyme-linked immunoassay (ELISA). Preeclamptic placentas secreted higher levels of IL-1β (P < 0.001), and a tendentious higher levels of IL-1Ra, mainly into the maternal circulation, as compared with normotensive placentas, although no differences in IL-1β:IL-1Ra ratio were detected. However, there was only tendentious increase in the secretion levels of IL-1β or IL-1Ra into the fetal circulation of preeclamptic placentas, when compared with normotensive placentas. Administration of MgSO(4) to preeclamptic placentas resulted in an attenuation of the increased secretion of IL-1β into the maternal circulation (P < 0.001), and in a tendentious reduction in IL-1Ra. However, IL-1β:IL-1Ra ratio in preeclamptic placentas was not affected by MgSO(4). Interestingly, exposure of normotensive placenta to MgSO(4) resulted only in increased levels of IL-1Ra in the maternal circulation, without affecting IL-1β levels or IL-1β:IL-1Ra ratio. These findings suggest that the placenta may contribute to the elevation in serum IL-1β and IL-1Ra in preeclampsia by increased secretion of these cytokines into the maternal circulation, and that MgSO(4) is able to attenuate this increased secretion of IL-1β, and possibly IL-1Ra, in preeclampsia.

FIG. 1.

IL-1β levels in the fetal (A) and the maternal (B) circulations of normotensive (n=3) and preeclamptic (n=5) placentas after perfusion with control medium (without MgSO₄). Results are displayed as mean±SE. Statistical significance was determined using 2-way ANOVA and Bonferroni post tests (***P<0.001). IL-1β, interleukin-1β; MgSO₄, magnesium sulfate; SE, standard error; ANOVA, analysis of variance.

FIG. 2.

IL-1Ra levels in the fetal (A) and the maternal (B) circulations of normotensive (n=3) and preeclamptic (n=5) placentas after perfusion with control medium (without MgSO₄). Results are displayed as mean±SE. Statistical significance was determined using 2-way ANOVA and Bonferroni post tests. IL-1Ra, interleukin-1 receptor antagonist.

FIG. 3.

IL-1β:IL-1Ra ratio in the fetal (A) and the maternal (B) circulations of normotensive (n=3) and preeclamptic (n=5) placentas after perfusion with control medium (without MgSO₄). Results are displayed as mean±SE. Statistical significance was determined using 2-way ANOVA and Bonferroni post tests.

FIG. 4.

IL-1β levels in the fetal (A) and the maternal (B) circulations of normotensive placentas after perfusion with control medium (without MgSO₄; n=3) or with medium containing MgSO₄ (6–7 mg%; n=3). Results are displayed as mean±SE. Statistical significance was determined using 2-way ANOVA and Bonferroni post tests.

FIG. 5.

IL-1β levels in the fetal (A) and the maternal (B) circulations of preeclamptic placentas after perfusion with control medium (without MgSO₄; n=5) or with medium containing MgSO₄ (6–7 mg%; n=4). Results are displayed as mean±SE. Statistical significance was determined using 2-way ANOVA and Bonferroni post tests (***P<0.001).

FIG. 6.

IL-1Ra levels in the fetal (A) and the maternal (B) circulations of normotensive placentas after perfusion with control medium (without MgSO₄; n=3) or with medium containing MgSO₄ (6–7 mg%; n=3). Results are displayed as mean±SE. Statistical significance was determined using 2-way ANOVA and Bonferroni post tests (*P<0.05; **P<0.01).

FIG. 7.

IL-1Ra levels in the fetal (A) and the maternal (B) circulations of preeclamptic placentas after perfusion with control medium (without MgSO₄; n=5) or with medium containing MgSO₄ (6–7 mg%; n=4). Results are displayed as mean±SE. Statistical significance was determined using 2-way ANOVA and Bonferroni post tests.

FIG. 8.

IL-1β:IL-1Ra ratio in the fetal (A) and the maternal (B) circulations of normotensive placentas after perfusion with control medium (without MgSO₄; n=3) or with medium containing MgSO₄ (6–7 mg%; n=3). Results are displayed as mean±SE. Statistical significance was determined using 2-way ANOVA and Bonferroni post tests.

FIG. 9.

IL-1β:IL-1Ra ratio in the fetal (A) and the maternal (B) circulations of preeclamptic placentas after perfusion with control medium (without MgSO₄; n=5) or with medium containing MgSO₄ (6–7 mg%; n=4). Results are displayed as mean±SE. Statistical significance was determined using 2-way ANOVA and Bonferroni post tests.