Women Serum Concentrations of the IL-10 Family of Cytokines and IFN-γ Decrease from the Third Trimester of Pregnancy to Active Labor

Abstract

Labor is regarded as increased myometrial activity with a regular contractility pattern. At this final stage of pregnancy, myometrial quiescence is lost, accompanied by altered immune homeostasis. It is well known that the interleukin (IL)-10 family of cytokines modulates immunological responses mainly in epithelial cells, including the endometrium. To investigate their inflammatory profile during labor, we performed a longitudinal study in a group of healthy pregnant women (n = 20) with uncomplicated pregnancies in the third trimester of pregnancy and during active labor. Blood was sampled from pregnant women in the third trimester (gestational age 32-38 weeks, mean 36 ± 2 weeks) and during active labor (39-41 weeks of gestation, mean 40 ± 1 weeks). Serum levels of several cytokines were measured using multiplex immunoassays for both stages, indicating that the concentrations of IL-10, IL-20, IL-22, IL-28A, and interferon (IFN)-γ were significantly decreased during active labor in comparison with third-trimester levels (p < 0.05). Our analysis did not find significant correlations between IL-10, IL-20, IL-22, IL-28A, and IFN-γ levels and gestational age. However, our data suggest that the systemic downregulation of several members of the IL-10 family of cytokines plays an important role in the activation of myometrial smooth cells associated with uterine contractions during active labor. Downregulation of this IL-10 family of cytokines seems to coincide with the well-reported functional progesterone withdrawal during labor. Likewise, lower plasma IFN-γ concentrations may indicate a role for IFN-γ in active labor.

Longitudinal plasma inflammatory proteome profiling during pregnancy in the Born into Life study

“…Wang et al 37 found increased level of IL-18 in pregnant women compared to non-pregnant women confirming our results of increased levels of IL-18 throughout pregnancy and postpartum compared to baseline. A few other longitudinal studies are in accordance with our result of a decrease in IL-10 between late pregnancy and postpartum 16,20,36 . In addition, another study found stability in IL-10 postpartum measured at multiple time-points 8 .…”

“…Chemokines control the homeostasis of the immune cells and represent a pro-inflammatory mediator. One of the most studied chemokines longitudinally in pregnancy is the IL-8 protein (also named CXCL-8) where several studies found no change during pregnancy 16,17,25 or from late pregnancy to postpartum 8,25 . In line with our U-shaped pattern between the time-points of IL-8 is Christian et al 23 who found decreased level of IL-8 during pregnancy but increased level postpartum.…”

“…A few studies have investigated longitudinal changes in proteins during pregnancy in healthy women [15][16][17][18][19][20] . However, most studies suffer from small sample sizes 15,16,[19][20][21][22][23][24][25] in selected study populations 15,17,24,25 . Some studies have included measurements postpartum 20,21,[23][24][25] in addition to those during pregnancy but no study has included an assessment before conception.…”

Neuroautonomic activity evidences parturition as a complex and integrated neuro–immune–endocrine process

“…). In a recent study, we reported that the systemic downregulation of several members of the IL‐10 cytokines family may play an important role in the stimulation of the myometrial smooth cells associated with uterine contractions of a woman in active labor . Accordingly, this immune downregulation seems to agree with the well‐reported functional progesterone withdrawal occurring at parturition .…”

“…In a recent study, we reported that the systemic downregulation of several members of the IL‐10 cytokines family may play an important role in the stimulation of the myometrial smooth cells associated with uterine contractions of a woman in active labor . Accordingly, this immune downregulation seems to agree with the well‐reported functional progesterone withdrawal occurring at parturition . It is well known that the ANS plays a major regulatory role of multiple complex physiological systems in the organism and it acts as a part of the neuroimmune response to sterile and nonsterile tissue injuries via the CAIP .…”