Macrophage migration inhibitory factor deficiency enhances immune response to Nippostrongylus brasiliensis.

Infections with helminth parasites are endemic in the developing world and are a target for intervention with new therapies. Macrophage migration inhibitory factor (MIF) is a cytokine with pleiotropic effects in inflammation and immune responses. We investigated the role of MIF in a naturally cleared model of helminth infection in rodents, Nippostrongylus brasiliensis. At day 7 postinfection, MIF-deficient (MIF-/-) mice had reduced parasite burden and mounted an enhanced type 2 immune response (Th2), including increased Gata3 expression and interleukin-13 (IL-13) production in the mesenteric lymph nodes (MLNs). Bone marrow reconstitution demonstrated that MIF produced from hematopoietic cells was crucial and Rag1-/- reconstitution provided direct evidence that MIF-/- CD4+ T cells were responsible for the augmented parasite clearance. MIF-/- CD4+ T cells produced less IL-6 postinfection, which correlated with enhanced Th2 responses. MIF-/- CD4+ T cells exhibited lower nuclear factor-κB activation, potentially explaining the reduction in IL-6. Finally, we demonstrated enhanced clearance of the parasite and Th2 response in wild-type mice treated with the MIF tautomerase inhibitor, sulforaphane, a compound found naturally found in cruciferous vegetables. These results are the first to describe the importance of the tautomerase enzyme activity in MIF function in N. brasiliensis infection.

Feeding at the Breast and Expressed Milk Feeding: Associations with Otitis Media and Diarrhea in Infants.

OBJECTIVE: To examine the associations of substance fed and mode of breast milk delivery with occurrence of otitis media and diarrhea in the first year of life. STUDY DESIGN: At 12 months postpartum, women (n = 813; 62% response) completed a questionnaire that assessed sociodemographics, infant occurrence of otitis media and diarrhea, and the timing of starting/stopping feeding at the breast, expressed milk, and formula. Women who intended to "bottle feed" exclusively were not recruited. Logistic and negative binomial regressions were conducted in the full sample (n = 491) and no-formula (n = 106) and bottle-only (n = 49) subsamples. RESULTS: Longer duration of expressed milk feeding was associated with increased odds of experiencing otitis media (6-month OR [OR6-month] 2.15, 95% CI 1.01-4.55) in the no-formula subsample. Longer durations of breast milk feeding (OR6-month 0.70, 95% CI 0.54-0.92; 6-month incidence rate ratio [IRR6-month] 0.74, 95% CI 0.63-0.91), and feeding at the breast (OR6-month 0.70, 95% CI 0.54-0.89; IRR6-month 0.74, 95% CI 0.63-0.88) were associated with less diarrhea, and longer formula feeding duration was associated with increased risk of diarrhea (IRR6-month 1.34, 95% CI 1.13-1.54) in the full sample. CONCLUSION: Substance fed and mode of breast milk delivery have different contributions to infant health depending on the health outcome of interest. Feeding at the breast may be advantageous compared with expressed milk feeding for reducing the risk of otitis media, and breast milk feeding compared with formula may reduce the risk of diarrhea.

Fatty acid composition in the mature milk of Bolivian forager-horticulturalists: controlled comparisons with a US sample.

Breast milk fatty acid (FA) composition varies greatly among individual women, including in percentages of the long-chain polyunsaturated FAs (LCPUFA) 20:4n-6 (arachidonic acid, AA) and 22:6n-3 (docosahexaenoic acid, DHA), which are important for infant neurological development. It has been suggested that owing to wide variation in milk LCPUFA and low DHA in Western diets, standards of milk FA composition should be derived from populations consuming traditional diets. We collected breast milk samples from Tsimane women at varying lactational stages (6-82 weeks). The Tsimane are an indigenous, natural fertility, subsistence-level population living in Amazonia Bolivia. Tsimane samples were matched by lactational stage to samples from a US milk bank, and analysed concurrently for FA composition by gas-liquid chromatography. We compared milk FA composition between Tsimane (n = 35) and US (n = 35) mothers, focusing on differences in LCPUFA percentages that may be due to population-typical dietary patterns. Per total FAs, the percentages of AA, DHA, total n-3 and total n-6 LCPUFA were significantly higher among Tsimane mothers. Mean percentages of 18:2n-6 (linoleic acid) and trans FAs were significantly higher among US mothers. Tsimane mothers' higher milk n-3 and n-6 LCPUFA percentages may be due to their regular consumption of wild game and freshwater fish, as well as comparatively lower intakes of processed foods and oils that may interfere with LCPUFA synthesis.

Adiponectin is present in human milk and is associated with maternal factors.

BACKGROUND: Previous studies have shown that human milk has a role in the gastrointestinal, neural, and immune development of neonates. If present in milk, adiponectin would be a promising candidate for influencing infant development, given its metabolic functions. OBJECTIVES: Our objectives were to determine whether adiponectin is present in human milk and to characterize maternal factors associated with potential variation in milk adiponectin concentrations. DESIGN: We quantified adiponectin concentrations in human milk samples from donors to the Cincinnati Children's Research Human Milk Bank and randomly selected participants in a cohort study in Mexico City funded by the National Institutes of Health. Using cross-sectional and longitudinal data, we examined milk adiponectin concentrations in relation to lactation duration, maternal body mass index (BMI; in kg/m(2)), and ethnicity. RESULTS: Adiponectin was detected in human skim milk (range: 4.2-87.9 ng/mL). In cross-sectional and longitudinal analyses, duration of lactation was negatively associated with milk adiponectin concentrations (beta = -0.059 +/- 0.024 and -0.059 +/- 0.007, respectively; P < 0.02 for both). Maternal postpregnancy BMI was positively associated with milk adiponectin concentrations (beta = 0.08 +/- 0.02, P < 0.0001; longitudinal analysis). Mexican mothers had lower median milk adiponectin concentrations at 1 mo than did the non-Hispanic white subjects from Cincinnati (11.5 and 19.8 ng/mL; P = 0.003). CONCLUSIONS: Adiponectin is present in human milk and its concentrations are associated with duration of lactation, maternal adiposity, and ethnicity. Given the importance of adiponectin in inflammation, insulin sensitivity, and fatty acid metabolism, future studies should examine milk adiponectin's role in infant metabolic development.