Decreased cord blood IL-4, IL-13, and CCR4 and increased TGF-beta levels after fish oil supplementation of pregnant women.

BACKGROUND: Altered intakes of n-3 and n-6 polyunsaturated fatty acids were suggested to modulate allergic disease, but intervention trials yielded inconclusive results. Because allergies are primed in early infancy and in utero, the fetus might be more accessible to nutritional intervention strategies. OBJECTIVE: We sought to investigate how supplementation of pregnant women with a fish oil (FO) preparation modulates allergy-related immune parameters in mothers and offspring. METHODS: We performed a multicenter, randomized, double-blind, placebo-controlled trial. Three hundred eleven pregnant women received daily either FO with 0.5 g of docosahexaenoic acid and 0.15 g of eicosapentaenoic acid, 400 mug of methyl-tetra-hydrofolic acid, both, or placebo from the 22nd gestational week. T(H)1/T(H)2-related molecules were quantified in 197 maternal and 195 cord blood samples by using real-time RT-PCR. Data are given as geometric means [95% CIs]. RESULTS: FO supplementation was associated with increased TGF-beta mRNA in maternal (0.85 [0.8-0.89]; placebo: 0.68 [0.64-0.72]) and cord blood (0.85 [0.81-0.9]; placebo: 0.75 [0.71-0.79]). IL-1 (0.69 [0.66-0.73]; placebo: 0.83 [0.79-0.88]) and IFN-gamma (0.54 [0.51-0.57]; placebo: 0.65 [0.61-0.69]) were decreased in mothers only (P < .001). Cord blood mRNA levels of IL-4 (0.54 [0.52-0.57]; placebo: 0.64 [0.61-0.68]), IL-13 (0.61 [0.58-0.65]; placebo: 0.85 [0.80-0.89]), CCR4 (0.70 [0.67-0.73]; placebo: 0.88 [0.84-0.92]; all P < .001), and natural killer (P < .001) and CCR3+CD8+ T cells (P < .04) were decreased in the FO group. CONCLUSION: Supplementation with FO during pregnancy is associated with decreased mRNA levels of T(H)2-related molecules in the fetus and decreased maternal inflammatory cytokines. We speculate that both effects are mediated by TGF-beta.

Deleted in Malignant Brain Tumors 1 (DMBT1) is present in hyaline membranes and modulates surface tension of surfactant.

BACKGROUND: Deleted in Malignant Brain Tumors 1 (DMBT1) is a secreted scavenger receptor cysteine-rich protein that binds various bacteria and is thought to participate in innate pulmonary host defense. We hypothesized that pulmonary DMBT1 could contribute to respiratory distress syndrome in neonates by modulating surfactant function. METHODS: DMBT1 expression was studied by immunohistochemistry and mRNA in situ hybridization in post-mortem lungs of preterm and full-term neonates with pulmonary hyaline membranes. The effect of human recombinant DMBT1 on the function of bovine and porcine surfactant was measured by a capillary surfactometer. DMBT1-levels in tracheal aspirates of ventilated preterm and term infants were determined by ELISA. RESULTS: Pulmonary DMBT1 was localized in hyaline membranes during respiratory distress syndrome. In vitro addition of human recombinant DMBT1 to the surfactants increased surface tension in a dose-dependent manner. The DMBT1-mediated effect was reverted by the addition of calcium depending on the surfactant preparation. CONCLUSION: Our data showed pulmonary DMBT1 expression in hyaline membranes during respiratory distress syndrome and demonstrated that DMBT1 increases lung surface tension in vitro. This raises the possibility that DMBT1 could antagonize surfactant supplementation in respiratory distress syndrome and could represent a candidate target molecule for therapeutic intervention in neonatal lung disease.

Docosahexaenoic acid supply in pregnancy affects placental expression of fatty acid transport proteins.

BACKGROUND: Better understanding of the mechanisms involved in docosahexaenoic acid (DHA) transfer to the neonate may contribute to improve dietary support for infants born prematurely to mothers with placental lipid transport disorders. OBJECTIVE: We studied whether DHA supplements modify the messenger RNA (mRNA) expression of placental lipid transport proteins to allow a selective transfer of DHA to the fetus. DESIGN: Healthy pregnant women (n = 136) received, in a double-blind randomized trial, 500 mg DHA + 150 mg eicosapentaenoic acid, 400 microg 5-methyl-tetrahydrofolic acid, 500 mg DHA + 400 microg 5-methyl-tetrahydrofolic acid, or placebo during the second half of gestation. We analyzed the fatty acid composition of maternal and cord blood phospholipids and of placenta; we quantified placental mRNA expression of fatty acid-transport protein 1 (FATP-1), FATP-4, FATP-6, fatty acid translocase, fatty acid-binding protein (FABP) plasma membrane, heart-FABP, adipocyte-FABP, and brain-FABP. RESULTS: The mRNA expression of the lipid carriers assayed did not differ significantly between the 4 groups. However, the mRNA expression of FATP-1 and FATP-4 in placenta was correlated with DHA in both maternal plasma and placental phospholipids, although only FATP-4 expression was significantly correlated with DHA in cord blood phospholipids. Additionally, the mRNA expression of several membrane lipid carriers was correlated with EPA and DHA in placental triacylglycerols and with EPA in placental free fatty acids. CONCLUSIONS: Correlation of the mRNA expression of the membrane placental proteins FATP-1 and especially of FATP-4 with maternal and cord DHA leads us to conclude that these lipid carriers are involved in placental transfer of long-chain polyunsaturated fatty acids.