J. Hale

Clinical effects of probiotics are associated with increased interferon‐γ responses in very young children with atopic dermatitis

Background We recently demonstrated that administration of probiotics resulted in significant clinical improvement in very young children with moderate‐to‐severe atopic dermatitis (AD). The purpose of this study was to determine the underlying immunological effects that are associated with these apparent clinical benefits.

Effects of probiotic supplementation for the first 6 months of life on allergen- and vaccine-specific immune responses

Background A reduction in microbial burden during infancy when allergen‐specific memory is evolving has become a prominent explanation for the allergy epidemic.

FOXP3 mRNA expression at 6 months of age is higher in infants who develop atopic dermatitis, but is not affected by giving probiotics from birth

Factors that influence immune regulation in early life may be implicated in the rise in allergic disease, including reduced microbial burden. The aim of the study was to examine the infant regulatory T‐cell function in relation to (a) probiotic supplementation for the first 6 months of life and (b) the subsequent development of an early allergic phenotype. Two hundred and thirty‐one allergic, pregnant women were recruited into a randomized, controlled trial. The infants received either a probiotic or placebo daily for the first 6 months of life. One hundred and seventy‐eight children completed the study, with blood samples available from 118 (60 placebo; 58 probiotic). CD4+CD25+CTLA4+T‐regulatory phenotype and allergen‐induced FOXP3 mRNA expression were compared in relation to this intervention as well as according to evidence of early disease (atopic dermatitis). The administration of probiotics was not associated with any significant differences in the proportion of circulating CD4+CD25+CTLA4+cells, or in the resting expression of FOXP3. There were also no relationships between these parameters and patterns of gut colonization, and this probiotic did not reduce the risk of atopic dermatitis. Children who developed atopic dermatitis (n = 36/118) had significantly higher induced FOXP3 expression following stimulation with both house dust mite (HDM) (p = 0.017) and ovalbumin (OVA) allergens (p = 0.021) than those that did not develop atopic dermatitis. Although this relationship was seen in both the probiotic and placebo groups, it was more pronounced in the probiotic group. However, regression analysis demonstrated that higher allergen‐induced FOXP3 expression was predicted by the presence of atopic dermatitis (p = 0.018) rather than probiotics supplementation (p = 0.217). The higher levels of allergen‐induced FOXP3 in atopic dermatitis suggest activation of these compensatory mechanisms rather than a primary defect in this pathway. Probiotic supplementation and gut colonization did not appear to substantially modify these regulatory pathways, or the risk of developing atopic dermatitis.

Atopic dermatitis in young children is associated with impaired interleukin‐10 and interferon‐γ responses to allergens, vaccines and colonizing skin and gut bacteria

Background A significant proportion of children with food allergy and more severe forms of atopic dermatis (AD) go on to develop persistent forms of allergic disease such asthma. Defining immune dysregulation in these children will be of great value in understanding disease pathogenesis.

Evaluation of the effects of probiotic supplementation from the neonatal period on innate immune development in infancy

Background Activation of the innate immune system by microbial stimulation is believed to be critical for normal immune maturation, and there has been speculation that these pathways are important for inhibiting allergic‐immune responses.

Supplementation with vitamins C, E, β‐carotene and selenium has no effect on anti‐oxidant status and immune responses in allergic adults: a randomized controlled trial

Background Anti‐oxidants are of growing interest in early treatment and prevention of allergic diseases in early life, but the effects on allergen‐specific immune responses need to be documented further before intervention studies in infants are undertaken. The aim of this study in adults was to determine the effects of dietary anti‐oxidants on allergen‐specific immune responses in sensitized individuals.

The effects of maternal smoking on early mucosal immunity and sensitization at 12 months of age

With the dramatic rise in asthma and respiratory disease, there is an urgent need to determine the effects of common environmental exposures on early immune development. In this study, we examined the effects of maternal smoking as a major adverse exposure in early life, on mucosal immune function and allergen sensitization in the first year of life. A cohort of 60 smokers and 62 non‐smokers was recruited in pregnancy, and followed prospectively at 3 and 12 months of age for saliva collection [for immunoglobulin (Ig) A measurements], urine collection (for cotinine levels) and clinical assessments (for allergy and infection history). Allergen skin‐prick tests were also performed at 12 months of age. Specific IgA to common colonizing bacteria was measured on saliva samples, including pneumococcal polysaccharide (PS) serotype 14 and non‐typeable Haemophilus influenza (NTHI) outer membrane protein 6 (OMP6). Eighty‐two mothers and their infants completed the 12‐month follow‐up period – 56 in the maternal non‐smoking group and 26 in the maternal smoking group. Maternal smoking was associated with significantly higher total infant salivary IgA at 12 months of age (p = 0.026), and more chronic upper respiratory tract symptoms (p = 0.012). However, there were no differences in the level of specific IgA antibodies to common colonizing bacteria (pneumococcal PS serotype 14 and NTHI OMP6). In general, the IgA levels at 12 months were higher in children who had more chest infections in the first year (Kendalls tau b, 0.282; p = 0.003). There was also a trend of lower respiratory tract symptoms (wheeze) (p = 0.142) in infants of smokers. There were no effects of maternal smoking on the rates of allergen sensitization, atopic dermatitis and food allergy at 12 months of age. In conclusion, maternal smoking did not inhibit the production of anti‐microbial IgA, suggesting that other factors are responsible for the increased susceptibility to infection in these infants. The increased mucosal inflammation in these children was not associated with effects on early allergy propensity.

Associations between antioxidant status, markers of oxidative stress and immune responses in allergic adults

Background There has been growing interest in the role of antioxidant function in controlling inflammatory disease states, such as allergy. This study investigated the relationship between antioxidant status, markers of airways inflammation [exhaled nitric oxide (eNO)], oxidative stress (F2 isoprostanes) and immune responses in allergic adults.

Pregnancy IFN‐γ responses to foetal alloantigens are altered by maternal allergy and gravidity status

Background:  During pregnancy, variations in maternal–foetal cellular interactions may influence immune programming. This study was carried out to determine if maternal responses to foetal alloantigens are altered by maternal allergic disease and/or previous pregnancies.

Modulation of in vivo and in vitro cytokine production over the course of pregnancy in allergic and non-allergic mothers.

Breckler LA, Hale J, Jung W, Westcott L, Dunstan JA, Thornton CA, Prescott SL. Modulation of in vivo and in vitro cytokine production over the course of pregnancy in allergic and non‐allergic mothers.
Pediatr Allergy Immunol 2010: 21: 14–21.
© 2009 The Authors
Journal compilation