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.

Specialized NK cells are recruited in high numbers to the mammalian embryo implantation sites, yet remain pregnancy compatible. It is not well understood whether uterine NK (uNK) cells become adversely activated and mediate fetal demise, a common complication of early pregnancy. In this study we show that mating of IL-10^−/− mice resulted in fetal resorption or intrauterine growth restriction in response to very low doses of LPS. Pregnancy in congenic wild-type mice was normal even at 10-fold higher LPS doses. Fetal resorption in IL-10^−/− mice was associated with a significant increase in uNK cell cytotoxic activation and invasion into the placenta. Depletion of uNK cells, TNF-α neutralization, or IL-10 administration rescued pregnancy in LPS-treated IL-10^−/− animals. Our results identify an immune mechanism of fetal demise involving IL-10 deficiency, NK cells, and inflammation. These results may provide insight into adverse pregnancy outcomes in humans.

Background: Human milk, which contains compounds beneficial to infants, is often expressed and stored before use. Changes in its antioxidant activity with storage have not been studied. Objectives: To measure antioxidant activity of fresh, refrigerated (4°C), and frozen human milk (−20°C), stored for two to seven days; to compare the antioxidant activity of milk from mothers delivering prematurely and at term; to compare the antioxidant activity of infant formulas and human milk. Methods: Sixteen breast milk samples (term and preterm) were collected from mothers within 24 hours of delivery and divided into aliquots. Fresh samples were immediately tested for antioxidant activity, and the rest of the aliquots were stored at −20°C or 4°C to be analysed at 48 hours and seven days respectively. The assay used measures the ability of milk samples to inhibit the oxidation of 2,2′-azino-di-3-(ethylbenzthiazolinesulphonate) to its radical cation compared with Trolox. Results: Antioxidant activity at both refrigeration and freezing temperatures was significantly decreased. Freezing resulted in a greater decrease than refrigeration, and storage for seven days resulted in lower antioxidant activity than storage for 48 hours. There was no difference in milk from mothers who delivered prematurely or at term. Significantly lower antioxidant activity was noted in formula milk than in fresh human milk. Conclusions: To preserve the antioxidant activity of human milk, storage time should be limited to 48 hours. Refrigeration is better than freezing and thawing.