Antioxidants and allergic disease: a case of too little or too much?

Speculation persists as to the possible role, if any, of dietary antioxidants in allergic disease. While it has been hypothesized that the recent increase in allergic disease is a consequence of declining dietary antioxidant intake, an alternative hypothesis proposes that the increase in allergic disease is due to increasing antioxidant intake. Dietary trends are conflicting; the intake of some antioxidants has declined, for others intakes are likely to have increased. Animal model studies demonstrate that antioxidant supplementation at the time of primary and subsequent allergen exposure attenuates allergic inflammatory responses. The data from human studies are less clear. Observational epidemiological studies of humans are beset by several methodological limitations associated with the assessment of diet and predominantly focus on asthma. Most observational studies report potentially beneficial associations between dietary antioxidants and allergic outcomes, but a small minority report potentially adverse associations. Human intervention studies suggest that single antioxidant supplements confer minimal, if any clinical benefit in adults with asthma, however, there is still scope for studies in children, atopic dermatitis, allergic rhinitis (AR) and of antioxidant combinations. More recently, it has been suggested that dietary antioxidants in the developmental context of fetal and infant development influence the development childhood asthma and atopic sensitization possibly by affecting the first interactions between the neonatal immune system and allergens. While a small number of birth cohort studies have reported potentially beneficial associations between maternal intake of some antioxidants during pregnancy and childhood asthma, there is very limited data suggesting associations between maternal antioxidant intake and childhood atopic dermatitis and AR. The available epidemiological, animal, molecular and immunological data suggest that there are associations between antioxidants and asthma and to a much lesser extent, atopic dermatitis and AR. However, the exact nature of the relationships and the potential for therapeutic intervention remain unclear.

Early childhood wheezing symptoms in relation to plasma selenium in pregnant mothers and neonates.

OBJECTIVE: Reduced dietary selenium intake has been linked to the development of asthma. We have investigated whether childhood wheezing symptoms, and asthma up to the age of 5 years are associated with plasma selenium and erythrocyte glutathione peroxidase (GPx) concentrations in pregnant mothers and neonates. METHODS: Two thousand pregnant women were recruited and their 1924 singleton children followed up. Plasma selenium and erythrocyte GPx concentrations were measured in maternal blood during early pregnancy (12 weeks gestation) and in neonatal cord blood. Cohort children were followed up at 1, 2 and 5 years using a respiratory symptom questionnaire and at 5 years children were also invited for spirometry and skin-prick test (SPT). Maternal and neonatal plasma selenium and erythrocyte GPx were related to the childhood outcomes of wheezing, and asthma. RESULTS: At 2 years 1282 children were followed up. At 5 years symptom data were available for 1167 children, 700 children were SPT tested, and forced expiratory volume in 1 s (FEV(1)) was measured in 478. Maternal plasma selenium concentration during early pregnancy was inversely associated with wheezing (odds ratio per 10 microg/kg plasma selenium 0.86, 95% confidence interval 0.76-0.97), and consulting a doctor because of wheeze (0.79, 0.69-0.93) in the second year of life. Cord plasma selenium was also inversely associated with wheezing (0.67, 0.47-0.96), and consulting a doctor because of wheeze (0.62, 0.41-0.93) in the second year of life. By age 5 these associations had disappeared. Maternal and neonatal erythrocyte GPx concentrations were not associated with any childhood outcomes at 2 or 5 years. CONCLUSION: The selenium status of mothers during early pregnancy, and neonates is associated with early childhood wheezing but not asthma or atopic sensitization, furthermore, this association is absent by the age of 5 years.

In utero priming of allergen-specific helper T cells.

BACKGROUND: Allergic diseases are major health problems in developed countries. Cord blood mononuclear cells (CBMC) at birth can proliferate after stimulation with allergen and this has led to the widespread view that the sensitization of the fetal immune system by allergens is a key determinant in establishing immunological bias towards allergy. However, the notion that the immune system can be primed by allergen in utero remains unproven. Determination of the CD45 isoform of responding T helper cells is an established method of determining the activation status of responding T helper cells because unsensitized cells express CD45RAhigh and previously sensitized cells CD45ROhigh. OBJECTIVE: To determine if sensitization of allergen-specific T helper cells can occur in utero by determining the CD45 isoform of CBMC proliferating in response to allergen. METHODS: CBMC proliferative responses were measured after stimulation in culture with a panel of allergens, mitogen and control antigen. To ascertain whether any responding T helper cells had been primed in utero, depletion experiments established whether they carried the CD45ROhigh marker of previous activation or the CD45RAhigh marker of unstimulated T cells. RESULTS: CBMC from a high proportion of 223 randomly selected neonates were stimulated to proliferate in vitro by allergens, with 76% responding to timothy grass pollen. In 50% of such responses to timothy grass, the CD45 isoform of the T cells that proliferate indicated that they had been previously activated. However, the remaining 50% of responses to timothy grass were mediated by previously unstimulated T cells. Proliferative responses mediated by CBMC sensitized in utero tended to be greater in magnitude than those mediated by unsensitized cells (P = 0.08). Seventy-five per cent of CBMC samples proliferated after stimulation with mycobacterial PPD and, as in BCG-vaccinated adults, all such CBMC proliferative responses at birth were predominately mediated by sensitized cells. CONCLUSION: Allergen- and antigen-specific Th cells can be primed in utero.

Measurement of T-helper cytokines secreted by cord blood mononuclear cells in response to allergens.

It has been proposed that in utero factors may predispose towards the development of childhood atopy. To test this hypothesis, it will be necessary to measure T-helper cell (Th) cytokines secreted by human cord blood mononuclear cells (CBMC) stimulated by allergens. However, to date, it has proven impossible to measure allergen-specific CBMC secretion of the key Th cytokine interleukin-4 (IL-4) using conventional sandwich ELISA techniques. We report for the first time the successful measurement of IL-4 secreted by CBMC stimulated by the allergens timothy grass pollen and house dust mite extract. The method is an adaptation of a novel cell-based ELISA (celELISA), which demonstrated an increased (up to 20-fold) sensitivity to detect IL-4. The method is simple, precise, is no more costly than a conventional ELISA, and can identify individuals in a general population whose CBMC exhibit different cytokine biases in response to allergens. The frequency distribution of IL-4 and interferon-gamma (IFN-gamma) CBMC responses to allergens in the general population approximates to a log-normal distribution, which will permit the application of linear regression techniques in the identification of in utero factors which influence Th bias.