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.
We asked whether a single-dose fetal treatment strategy using betamethasone plus either a long-acting beta2 agonist (formoterol) or betamethasone plus agents that elevate intracellular cyclic adenosine monophosphate (isobutyl methylxanthine and dibutyryl-cyclic adenosine monophosphate) would augment the effects of prenatal betamethasone on postnatal lung function. Preterm lambs were treated with 0.5 mg/kg betamethasone or betamethasone plus the other agents and delivered 48 h after treatment. The postnatal lung function as assessed by compliance, ventilatory efficiency, and lung volumes at 40 min of age was improved by prenatal betamethasone and improved further by combination treatment, although the augmented responses were not significantly greater than with betamethasone alone. Fatty acid synthase protein and enzymatic activity were not increased by betamethasone or combined treatments, in contrast to responses reported for other animal models. There were no effects of glucocorticoids or the combined treatments on surfactant. Stimulation of the beta2 agonist system did not augment postnatal lung function significantly above that noted for betamethasone alone with the agents, doses, and duration of exposures tested.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.