Spontaneous and LPS-induced secretion of cytokines by villous chorion tissue

Abstract

Secretion of IL-1alpha, IL-1beta, IL-6, IL-10, and TNF-alpha cytokines by villous chorion cultures (7-14 weeks) during normal pregnancy and in spontaneous abortions was studied. Secretion of IL-1alpha and IL-6 increased 4.5 and 7.3 times in miscarriages, while secretion of IL-1beta, IL-10, and TNF-alpha decreased. LPS stimulated the production of IL-1alpha and IL-6 in samples obtained during surgical abortion. LPS stimulated IL-1alpha and TNF-alpha secretion in miscarriages, while the level of IL-6 production decreased significantly. It is hypothesized that increased production of IL-1alpha and IL-6 and attenuation of the antiinflammatory effect of IL-10 play an important role in the pathogenesis of miscarriages at early stages of gestation. The results suggest that cytokine regulation of the fetus rejection is different at early and late stages of gestation.

Primary HSV-2 Infection in Early Pregnancy Results in Transplacental Viral Transmission and Dose-Dependent Adverse Pregnancy Outcomes in a Novel Mouse Model

“…Additionally, low-grade inflammation in the placenta, as observed with low doses of HSV-2 in our study, has been observed in pregnancies complicated by maternal obesity that result in adverse pregnancy outcomes, including congenital abnormalities and fetal macrosomia, in the absence of more severe outcomes [63,64]. Further, in a study conducted using first trimester placental tissues obtained from normal pregnancies and spontaneous abortions, only placental tissues from spontaneous abortions were associated with unstimulated production of inflammatory mediators [65]. This may point to a role of other placental factors in enhancing pro-inflammatory cytokine production, which underlies severe placental pathology and fetal death, as observed following high-dose infection in our study.…”

Progesterone Interactions with the Cervix: Translational Implications for Term and Preterm Birth

“…In mouse pregnancy, preterm birth tended to be characterized by increased levels of several proinflammatory factors, while there was a downregulation of Il-10 [73]. Likewise in chorionic villous cultures from early miscarriages, Il-10 was attenuated while IL-1a and Il-6 were elevated [74]. In the presence of intra-amniotic infection at term, there was a higher level of amniotic fluid Il-10 than among term pregnancies without infection, and in both term and preterm birth, the Il-10 was elevated [75] which on the surface seems counterintuitive but may reflect a feedback mechanism to dampen the proinflammatory reaction after parturition.…”

Placental Villous Expression of TNFα and IL‐10 and Effect of Oxygen Tension in Euploid Early Pregnancy Failure

“…[4][5][6] Cytokines are pleiotropic polypeptides involved in the modulation of immune responses and inflammatory reactions which take place at the feto-maternal interface in both normal and abnormal pregnancy. [9][10][11] Previous studies have measured the partial pressure of oxygen (O 2 ) within the human placenta in vivo. 8 There is evidence for a shift in Th1 (TNFα): Th2 (IL-10) ratio in early pregnancy loss in the maternal circulation and placenta.…”

“…8 There is evidence for a shift in Th1 (TNFα): Th2 (IL-10) ratio in early pregnancy loss in the maternal circulation and placenta. [9][10][11] Previous studies have measured the partial pressure of oxygen (O 2 ) within the human placenta in vivo. During early first trimester, there is physiologically low O 2 (<10%) as opposed to ambient O 2 tension of 21%.…”