Gestational Age-Dependent Expression of IL-10 and Its Receptor in Human Placental Tissues and Isolated Cytotrophoblasts

TLDR

Placental local regulation is believed to control antifetal immune responses, with gestational programming potentially influencing this immunity. The study hypothesizes that IL‑10 production by the placenta varies with gestational age. The authors measured IL‑10 and its receptor expression in placental explants and isolated cytotrophoblasts across gestational ages, comparing to other cytokines. IL‑10 is highly expressed in first and second trimester placentas but declines at term before labor, while pro‑inflammatory cytokines rise during labor, indicating a gestational age‑dependent regulation of IL‑10 that may contribute to parturition.

Abstract

Abstract Control of antifetal immune responses is thought to be regulated locally by the placenta. Because the physiologic programming of the placenta across gestation is likely to influence the local immunity, we hypothesize that a potent anti-inflammatory cytokine such as IL-10 may be produced in a gestational age-dependent manner. In the present study, we examined the expression of IL-10 and its receptor in placental explants or freshly isolated cytotrophoblasts from different gestational ages and compared it with the expression profiles of other cytokines. First and second trimester placental tissues from normal pregnancies predominantly expressed IL-10, whereas the levels of IL-2, IL-4, and IFN-γ were mostly below detection throughout pregnancy. The expression of IL-10, but not its receptor, diminished significantly in term placental tissues collected “before” the onset of labor and did not change appreciably “after” labor. On the other hand, TNF-α and IL-1β were significantly up-regulated in response to labor-associated conditions. IL-10 expression was transcriptionally attenuated at term as observed in cytotrophoblasts. In contrast to the placental cytokine milieu, autologous PBMCs, when activated with PHA, secreted significant amounts of IL-2, IL-4, IL-10, and IFN-γ, albeit with a statistically significantly enhanced IL-10 production in first trimester compared with age-matched nonpregnant women. These data suggest that IL-10 is expressed in the placenta in a gestational age-dependent manner and that its down-regulation at term may be an important mechanism underlying the subtle changes associated with parturition.