Immunological programming by breast milk creates an anti-inflammatory cytokine milieu in breast-fed infants compared to formula-fed infants.

Breast milk provides important maturational stimuli to an infant's developing immune system. However, data concerning the role of breast-feeding in reducing the risk of allergic disease remain contradictory. Previous studies have centred on comparative analyses of breast milk and formula compositions. We chose a slightly different angle, whereby we focused on the effects of the chosen diet on the infant himself, comparing the immune development of formula-fed and breast-fed children. The objective of the present study was to determine how the mode of feeding affects infant immunology. Altogether, eighteen formula-fed infants with limited breast-feeding for ,3 months and twenty-nine infants who were exclusively breast-fed for .3 months were included in the study. Concentrations of interferon g, TNF-a IL-10, IL-5, IL-4 and IL-2 were measured simultaneously from the same serum sample through use of a multiplexed flow cytometric assay at the ages of 1, 3, 6 and 12 months. Transforming growth factor ß2 (TGF-ß2) was measured using ELISA at the same time points. Serum TNF-a and IL-2 concentrations were significantly higher in formula-fed than in breast-fed infants during the first year of life (ANOVA, P=0·002). The serum concentrations of TGF-b were significantly lower in formula-fed than in breast-fed infants throughout the first year of life (ANOVA, P≤0·0001). Exclusive breast-feeding promotes an anti-inflammatory cytokine milieu, which is maintained throughout infancy. Such an immunological environment limits hyper-responsiveness and promotes tolerisation, possibly prohibiting the onset of allergic disease.

Maternal probiotic supplementation during pregnancy and breast-feeding reduces the risk of eczema in the infant.

BACKGROUND: Probiotics have shown promising potential in reducing the risk of eczema in infants. Optimal probiotic intervention regimen remains to be determined. OBJECTIVE: We investigated whether maternal probiotic supplementation during pregnancy and breast-feeding reduces the risk of developing eczema in high-risk infants. METHODS: This was a parallel, double-blind placebo-controlled trial of 241 mother-infant pairs. Mothers with allergic disease and atopic sensitization were randomly assigned to receive (1) Lactobacillus rhamnosus LPR and Bifidobacterium longum BL999 (LPR+BL999), (2) L paracasei ST11 and B longum BL999 (ST11+BL999), or (3) placebo, beginning 2 months before delivery and during the first 2 months of breast-feeding. The infants were followed until the age of 24 months. Skin prick tests were performed at the ages of 6, 12, and 24 months. RESULTS: Altogether 205 infants completed the follow-up and were included in the analyses. The risk of developing eczema during the first 24 months of life was significantly reduced in infants of mothers receiving LPR+BL999 (odds ratio [OR], 0.17; 95% CI, 0.08-0.35; P < .001) and ST11+BL999 (OR, 0.16; 95% CI, 0.08-0.35; P < .001). The respective ORs for chronically persistent eczema were 0.30 (95% CI, 0.12-0.80; P = .016) and 0.17 (95% CI, 0.05-0.56; P = .003). Probiotics had no effect on the risk of atopic sensitization in the infants. No adverse effects were related to the use of probiotics. CONCLUSION: Prevention regimen with specific probiotics administered to the pregnant and breast-feeding mother, that is, prenatally and postnatally, is safe and effective in reducing the risk of eczema in infants with allergic mothers positive for skin prick test.

Unique cytokine secretion profile in children with both type I diabetes and asthma distinct from that of solely diabetic or asthmatic children.

Asthma and type I diabetes are major causes of chronic illness in childhood which, according to the current paradigm, have mutually antagonistic immunopathologies. Nonetheless, the disorders appear to preferably coexist both on population and individual levels. To assess whether children with asthma and type I diabetes might have a common immunoregulatory defect. The spontaneous and anti-CD3+ anti-CD28-stimulated cytokine production patterns by peripheral blood mononuclear cells of 13 children with both asthma and diabetes, nine children with diabetes, 11 children with asthma and nine healthy children were assessed using cytometric bead assay. The spontaneous production of IFN-gamma, TNF-alpha and IL-10 by mononuclear cells in children with both asthma and diabetes was elevated compared to the other study groups (p=0.02, p=0.001 and p=0.04, respectively). Stimulation in vitro increased IL-10 secretion in solely diabetic (p=0.008), asthmatic (p=0.008) and healthy children (p=0.01), but not in children with both diseases (p=0.22). Children suffering from both diabetes and asthma display a unique cytokine secretion pattern, distinct from those of solely diabetic, asthmatic and healthy children. In particular, these children appear to have a defect in regulation of IL-10 secretion.

Identification of genes involved in the initiation of human Th1 or Th2 cell commitment.

The differentiation of naïve T helper (Th) cells is induced by TCR activation and IL-12/STAT4 or IL-4/STAT6 signaling pathways, forming Th1 and Th2 cells, respectively. In this study, oligonucleotide arrays were used to identify genes regulated during the initiation of human Th1 and Th2 cell differentiation at 2 and 6 h in presence or absence of immunosuppressive TGF-beta. As a result the immediate targets of IL-12, IL-4 and TGF-beta were identified. The effects of IL-12 at this early stage were minimal and consistent with the known kinetics of IL-12Rbeta2 expression. IL-4, however, was observed to rapidly regulate 63 genes, 26 of which were differentially expressed at both the 2- and 6-h time points. Of these IL-4 regulated genes, one-third have previously been observed to display expression changes in the later phases of the polarization process. Similarly to the key regulators, TBX21 and GATA3, the transcription factors SATB1, TCF7 and BCL6 were differentially regulated at the protein level during early Th1 and Th2 cell polarization. Moreover, the developing Th1 and Th2 cells were demonstrated to be responsive to the immunosuppressive TGF-beta and IL-10. In this study, a panel of novel factors that may be important regulators of the differentiation process was identified.