Direct infant UV light exposure is associated with eczema and immune development.

BACKGROUND: Suboptimal vitamin D levels during critical periods of immune development have emerged as an explanation for higher rates of allergic diseases associated with industrialization and residing at higher latitudes. OBJECTIVE: We sought to determine the effects of early postnatal vitamin D supplementation on infant eczema and immune development. METHODS: By using a double-blind randomized controlled trial, newborn infants were randomized to receive vitamin D supplementation (400 IU/d) or a placebo until 6 months of age. Some infants also wore personal UV dosimeters to measure direct UV light (290-380 nm) exposure. Infant vitamin D levels were measured at 3 and 6 months of age. Eczema, wheeze, and immune function outcomes were assessed at 6 months of age. RESULTS: At 3 (P < .01) and 6 (P = .02) months of age, vitamin D levels were greater for the vitamin D-supplemented group than the placebo group, but there was no difference in eczema incidence between groups. Infants with eczema were found to have had less UV light exposure (median, 555 Joules per square meter [J/m2; interquartile range, 322-1210 J/m2]) compared with those without eczema (median, 998 J/m2 [interquartile range, 676-1577 J/m2]; P = .02). UV light exposure was also inversely correlated with IL-2, GM-CSF, and eotaxin production to Toll-like receptor ligands. CONCLUSION: This study is the first to demonstrate an association between greater direct UV light exposures in early infancy with lower incidence of eczema and proinflammatory immune markers by 6 months of age. Our findings indicate that UV light exposure appears more beneficial than vitamin D supplementation as an allergy prevention strategy in early life.

Fatty acid status and antioxidant defense system in mothers and their newborns after salmon intake during late pregnancy.

OBJECTIVE: The aim of the present study was to assess the maternal and newborn status of erythrocyte fatty acids and the antioxidant defense system after the intake of two portions of salmon per week during late pregnancy. METHODS: Pregnant women (N = 123) were randomly assigned to continue their habitual diet, which was low in oily fish (control group, n = 61) or to consume two 150-g salmon portions per week (salmon group, n = 62) beginning at 20 wk of gestation and lasting until delivery. Fatty acids, selenium, and glutathione concentrations and antioxidant defense enzyme activities were measured in maternal erythrocytes at 20, 34, and 38 wk of pregnancy, and in cord erythrocytes collected at birth. Plasma concentrations of antioxidant molecules were measured. RESULTS: Compared with the control group, consuming salmon had little effect on erythrocyte fatty acids in either mothers or newborns. Components of the antioxidant defense system did not differ between groups. Glutathione peroxidase activity and the concentrations of tocopherols, retinol, and coenzyme Q10 were significantly lower in cord blood compared with maternal blood at week 38 in both groups. CONCLUSION: Maternal and newborn erythrocyte fatty acids are not strongly affected by the intake of two portions of salmon per week during the second half of pregnancy, although erythrocyte docosahexaenoic acid might be increased in newborns. Maternal and newborn antioxidant defense systems are not impaired by intake of salmon from 20 wk gestation.

Increased intake of oily fish in pregnancy: effects on neonatal immune responses and on clinical outcomes in infants at 6 mo.

BACKGROUND: Long-chain n-3 PUFAs found in oily fish may have a role in lowering the risk of allergic disease. OBJECTIVE: The objective was to assess whether an increased intake of oily fish in pregnancy modifies neonatal immune responses and early markers of atopy. DESIGN: Women (n = 123) were randomly assigned to continue their habitual diet, which was low in oily fish, or to consume 2 portions of salmon per week (providing 3.45 g EPA plus DHA) from 20 wk gestation until delivery. In umbilical cord blood samples (n = 101), we measured n-3 fatty acids, IgE concentrations, and immunologic responses. Infants were clinically evaluated at age 6 mo (n = 86). RESULTS: Cord blood mononuclear cell (CBMC) production of interleukin (IL)-2, IL-4, IL-5, IL-10, and tumor necrosis factor-α in response to phytohemagglutinin (PHA) and of IL-2 in response to Dermatophagoides pteronyssinus allergen 1 (Derp1) was lower in the salmon group (all P ≤ 0.03). In the subgroup of CBMCs in which an allergic phenotype was confirmed in the mother or father, IL-10 production in response to Toll-like receptor 2, 3, and 4 agonists, ovalbumin, salmon parvalbumin, or Derp1 and prostaglandin E(2) production in response to lipopolysaccharide or PHA was lower in the salmon group (all P ≤ 0.045). Total IgE at birth and total IgE, incidence and severity of atopic dermatitis, and skin-prick-test positivity at 6 mo of age were not different between the 2 groups. CONCLUSION: Oily fish intervention in pregnancy modifies neonatal immune responses but may not affect markers of infant atopy assessed at 6 mo of age. This trial is registered at clinicaltrials.gov as NCT00801502.

Does consumption of two portions of salmon per week enhance the antioxidant defense system in pregnant women?

Salmon is a rich source of marine n-3 fatty acids, which may increase oxidative stress and, in turn, could affect the antioxidant defense system in blood plasma and erythrocytes of pregnant women. The Salmon in Pregnancy Study provided two meals of salmon per week to pregnant women from week 20 of gestation; the control group maintained their habitual diet low in oily fish. Higher selenium and retinol plasma concentrations were observed after dietary salmon supplementation. Besides, a concomitant increase in selenium and glutathione concentration as well as glutathione peroxidase and reductase activities were detected as pregnancy progressed. However, tocopherols, retinol, ß-carotene, and coenzyme Q(10) decreased in late pregnancy. Collectively, our findings lead to the hypothesis that increased farmed salmon intake may increase antioxidant defenses during pregnancy. Clinical trials identifier NCT00801502.

Short-term infusion of a fish oil-based lipid emulsion modulates fatty acid status, but not immune function or (anti)oxidant balance: a randomized cross-over study.

BACKGROUND AND AIMS: Studies suggest clinical benefits of parenteral fish oil (FO), rich in n-3 polyunsaturated fatty acids (PUFAs), over soyabean oil (SO), rich in n-6 PUFAs, in patients with pro-inflammatory conditions such as sepsis and trauma. Because the mechanisms behind these observations remain unclear, the present study explored the effects of intravenous infusion of FO and SO on fatty acid incorporation, immune functions and (anti)oxidant balance in healthy human volunteers. METHODS: Saline, a SO emulsion and a FO emulsion were administered for one hour on three consecutive days at a rate of 0·2 g/kg BW/h to eight subjects in a randomized cross-over design with a 3-week interval between treatments. Plasma phospholipid and peripheral blood mononuclear cell (PBMC) fatty acid compositions, and leucocyte counts and functions were assessed prior to the first infusion (T = 0, baseline) and 1 day (T = 4, early effects) and 8 days (T = 11, late effects) after the third infusion. RESULTS: Fish oil infusion significantly increased n-3 PUFA proportions and decreased n-6 PUFA proportions in plasma phospholipids and PBMCs. There were no differences in immune functions or (anti)oxidant balance between treatments at any time. CONCLUSIONS: The present lipid infusion protocol appears to be safe and well tolerated and provides significant incorporation of n-3 PUFAs into plasma phospholipids and PBMCs. In the absence of overt inflammation, no direct effects of FO were observed on immune function or (anti)oxidant balance. This model may be useful to evaluate effects of parenteral lipids in other settings, for example in individuals displaying an inflammatory state.

ß-Hydroxy-ß-methylbutyrate modifies human peripheral blood mononuclear cell proliferation and cytokine production in vitro.

OBJECTIVE: The main objective was to investigate the potential immunomodulatory effects of ß-hydroxy-ß-methylbutyrate (HMB) in human cells. METHODS: Peripheral blood mononuclear cells were isolated from the blood of eight volunteers and assayed for proliferation, cell cycle progression, surface expression of CD25, intracellular expression of pERK1/2, and cytokine production after in vitro exposure to a range of HMB concentrations (0.1 to 10 mM). RESULTS: Above 1 mM, HMB decreased the extent of proliferation normally observed after stimulation by concanavalin A. The decrease was evident at 10 mM HMB, when the proliferation index was 50% reduced when compared with the absence of HMB. Cell cycle analysis demonstrated an increase in the proportion of cells at the G0-G1 phase at 10 mM HMB. CD25 and pERK1/2 expression were not related to the observed effect on proliferation. HMB affected the concentrations of all five cytokines measured following stimulation. Tumor necrosis factor-α concentration in the culture medium was reduced by ~35% at all HMB concentrations. Th1/Th2 cytokine production was modified toward a Th2 profile when HMB was at 1 or 10 mM. Thus, HMB at 10 mM impairs lymphocyte proliferation and progression through the cell cycle. The lowest concentration used here (0.1 mM) exerted some actions on cytokine production, including decreasing TNF-α production, but not on proliferation and cell cycle progression. CONCLUSION: HMB may be a useful agent to consider for modulation of immune function in specific situations.

Association of maternal smoking with increased infant oxidative stress at 3 months of age.

BACKGROUND: Cigarette smoke is a major source of free radicals and oxidative stress. With a significant proportion of women still smoking during pregnancy, this common and avoidable exposure has the potential to influence infant oxidative status, which is implicated in the increased propensity for airway inflammation and asthma. The aim of this study was to examine the effects of maternal smoking on markers of infant oxidative stress. METHODS: The level of oxidative stress (using urinary F2-isoprostanes as a marker of lipid peroxidation) was compared in infants of smokers (n = 33) and non-smokers (n = 54) at 3 months of age. These groups were balanced for maternal atopy and socioeconomic status. Infant urinary cotinine levels were also measured as an indicator of early postnatal cigarette smoke exposure. RESULTS: Maternal smoking was associated with significantly higher infant cotinine levels, despite the fact that most smoking mothers (83.8%) claimed not to smoke near their baby. Maternal smoking was associated with significantly higher markers of oxidative stress (F2-isoprostane) at 3 months of age. There was also a positive correlation between urinary F2-isoprostanes and infant urinary cotinine levels. CONCLUSIONS: Although this study does not separate the prenatal and postnatal effects of smoking, these findings indicate that environmental tobacco smoke in the early postnatal period adversely affects pro-oxidative/antioxidative status within weeks of life in very early infancy.

Maternal smoking in pregnancy: do the effects on innate (toll-like receptor) function have implications for subsequent allergic disease?

: Subtle increases in immaturity of immune function in early infancy have been implicated in the rising susceptibility to allergic disease, particularly relative impairment of type 1 interferon (IFN)-gamma responses in the neonatal period. Although genetic predisposition is a clear risk factor, the escalating rates of allergic disease in infancy suggest that environmental factors are also implicated. We previously showed that maternal smoking in pregnancy may impair neonatal IFN-gamma responses. Our more recent studies now indicate that this common avoidable toxic exposure is also associated with attenuation of innate immune function, with attenuated Toll-like receptor (TLR)-mediated microbial responses (including TLR-2, -3, -4, and -9 responses). Most notably, the effects were more marked if the mothers were also allergic. In this review, we discuss the significance of these observations in the context of the emerging hypothesis that variations in TLR function in early life may be implicated in allergic propensity. There is now growing evidence that many of the key pathways involved in subsequent T-cell programming and regulation (namely, antigen-presenting cells and regulatory T cells) rely heavily on microbe-driven TLR activation for maturation and function. Factors that influence the function and activity of these innate pathways in early life may contribute to the increasing predisposition for allergic disease. Although "cleaner" environments have been implicated, here we explore the possibility that other common environmental exposures (such as maternal smoking) could also play a role.

The relationship between persistent organic pollutants in maternal and neonatal tissues and immune responses to allergens: A novel exploratory study.

BACKGROUND: Modern persistent organic pollutants (POPs) contamination are logical candidates in the investigation of the, as yet, unexplained association between allergic disease and progressive industrialisation. POPs have been detected in human cord blood, placental tissues and breast milk, and the reported association between cord blood IgE levels and cord/placental POP levels has raised concerns about potential immunological effects in early life. METHODS: The initial aim of this study was to determine if POPs were detectable in maternal blood, cord blood, placental tissues, adipose tissue and breast milk samples from randomly selected Western Australian women (n = 31), where allergic disease is epidemic. Gas chromatography was used to detect polychlorinated biphenyl compounds [PCBs] (as Aroclor 1232, 1254, 1260) and organochlorine (OC) pesticides, including p,p'-DDT, p,p'-DDE, hexachlorobenzene (HCB), lindane, heptachlor epoxide, dieldrin and chlordane. Secondly, we assessed the relationship between POP levels detected in vivo and maternal and neonatal responses (cytokine and lymphoproliferation) to allergens and mitogens. RESULTS: Low level POP contamination was detected in adipose tissue and breast milk (but not in cord blood, maternal blood or placental tissues). The most ubiquitous compound found in over 90% of adipose tissues samples was a OC metabolite of DDT, p,p'-DDE (median 0.07 mg/kg; interquartile range [IQR] 0.05-0.12). However, the majority of other OC compounds were not detectable and PCB were not detectable in any samples. The three main residues detected in breast milk were p,p'-DDE (0.003 mg/l; 0.001-0.009), dieldrin (0.001 mg/l; 0.001-0.046) and HCB (0.001 mg/l; 0.001-0.001). These levels are significantly lower than reported over 20 years ago. There were no consistent relationships between POP levels in vivo and maternal or infant responses, with the exception of a significant inverse association (Spearman rank correlation: r = -0.406, p = 0.049) between maternal adipose tissue levels of OC p,p'-DDE and maternal T helper cell Type 1 interferon [IFN] gamma to mitogens. CONCLUSION: This study provides the first evidence (in Australia) since the early 1990's that adipose OC levels have continued to fall. The negligible levels in this randomly selected group are significantly lower than those previously recorded, suggesting that POP contamination (at biologically relevant levels) is not likely to be a major contributing factor in the increasing rates of allergy in Western Australia. However, the relationship between Th1 immune function and OC contamination is consistent with other reports and is worth investigating as a relevant factor in populations where OC contamination is greater.