Malin Fagerås Böttcher

Infants with eczema and sensitization to foods are recommended skin care and, if food allergy is proven, an elimination diet. Although most of these children tolerate foods before 3 yr of age, some children experience prolonged food allergy. To our knowledge, no prospective study has investigated the cytokine profile in food-sensitized eczematous children with prolonged food intolerance. The aim of the study was to prospectively investigate the development of cytokine production induced by food allergen in food-sensitized eczematous children who, at 41/2 yr of age, were allergic or tolerant to egg or milk. Twenty-one eczematous infants, [age 5 (3-10) months; median and range], sensitized to egg and/or milk were included, put on elimination diet and followed prospectively. At 41/2 yr of age, the children were defined as tolerant or allergic to egg and/or milk based on open or double-blind placebo-controlled food challenges. Peripheral blood mononuclear cells (PBMC) were isolated from the children on inclusion, after 6 wk of elimination diet, and at 3 and 41/2 yr of age. Ovalbumin, beta-lactoglobulin and tetanus toxoid-induced IL-4, -5, -10, -13 and IFN-gamma production from PBMC were analyzed with enzyme-linked immunosorbent assay. The IFN-gamma and IL-5 secretion induced by food allergen at 41/2 yr was higher in cell cultures from children who were allergic to egg or milk than in tolerant children. In food-allergic children, the levels of IFN-gamma and IL-5 were higher at 41/2 yr compared with inclusion levels, but this increase was generally not observed in the tolerant children who consumed milk and egg. In conclusion, immune cells from food-allergic children on an elimination diet respond with up-regulated T helper 1 and T helper 2 cytokine secretion induced by food allergen. We hypothesize that allergen elimination may influence the regulatory mechanisms maintaining balanced immune responses to innocuous food antigens.

The immunological composition of breast milk differs between mothers. The reasons for these differences and the consequences for the breast‐fed infants are poorly understood. The aim of this study was to evaluate the effect of probiotic Lactobacillus reuteri supplementation on the immunological composition of breast milk in relation to sensitization and eczema in the babies. Total IgA, secretory IgA (SIgA), TGF‐β1, TGF‐β2, IL‐10, TNF, soluble CD14 (sCD14), and Na/K ratios were analyzed in colostrum and mature milk obtained from women treated with L. reuteri (n = 54) or placebo (n = 55) from gestational week 36 until delivery. Bacteriological analyses of L. reuteri were performed in faecal samples of the mothers. The infants were followed prospectively for 2 yr regarding development of eczema and sensitization as defined by a positive skin prick test and/or circulating allergen‐specific IgE antibodies at 6, 12, and 24 months of age. Supplementation of L. reuteri during pregnancy was associated with low levels of TGF‐β2 and slightly increased levels of IL‐10 in colostrum. For TGF‐β2, this association was most pronounced in mothers with detectable L. reuteri in faeces. Infants receiving breast milk with low levels of TGF‐β2 were less likely to become sensitized during their first 2 yr of life. A similar trend was observed for development of IgE‐associated eczema. The levels of total IgA, SIgA, TGF‐β1, TNF, sCD14, and Na/K ratios in breast milk were not affected by the intake of L. reuteri. None of these parameters correlated with sensitization or development of eczema in the infant, except for high Na/K ratios that associated with increased risk of sensitization. Supplementation with L. reuteri during late pregnancy reduces breast milk levels of TGF‐β2, and low levels of this cytokine are associated with less sensitization and possibly less IgE‐associated eczema in breast‐fed infants.

Summary: Background The prevalence of atopic disease among children in the formerly socialist countries in Europe, with a life style similar to that prevailing in Western Europe 30–40 years ago, is low, whereas there has been a pronounced increase in industrialized countries over the last decades. The environment during infancy influences the risk of developing allergy for many years, perhaps even for life.Objective To investigate the development of allergen‐specific cytokine responses during the first 2 years of life in two geographically adjacent countries with marked differences in living conditions and incidence of atopic diseases, i.e. Estonia and Sweden.Methods The development of immune responses to food (β‐lactoglobulin (BLG) and ovalbumin (OVA)) and inhalant (cat and birch) allergens was studied from birth up to the age of 2 years in 30 Estonian and 76 Swedish infants. Clinical investigation and skin prick tests were performed and blood samples were obtained at birth and at 3, 6, 12 and 24 months.Results The levels of IL‐5, IL‐10 and IL‐13 secreted by peripheral blood mononuclear cells stimulated with BLG, OVA and cat allergen in Estonian and Swedish infants declined during the first 3 months of life. All cytokines then progressively increased in the Swedish infants, indicating the replacement of non‐specifically responding immature cord blood T cells with specific T memory cells, which are primed postnatally. The resurgence of allergen‐specific responses in the Estonian infants was less marked. These differences were particularly notable for birch‐specific T cell responses, which correlated with development of atopic disease in the Swedish children.Conclusions The development of specific T cell memory to food and inhalant allergens during the first 2 years of life differs between infants living in Sweden and Estonia, and mirrors the disparate patterns of expression of allergic disease which subsequently develops in the respective populations.

Atopic asthma is characterized by excessive T helper 2 (Th2)‐like immunity to allergens in the bronchial mucosa. The Th2‐cytokine interleukin (IL)‐4 induces IgE production, while the Th2‐cytokine IL‐5 promotes eosinophilic inflammation in the airways of asthmatics. Most asthmatics are atopic, but a subgroup is non‐atopic. We hypothesize that allergen‐induced Th2, particularly IL‐5, responses can be observed in peripheral blood in both atopic and non‐atopic asthmatic children but not in healthy control children. The aim of the present study was to determine IL‐4, IL‐5, IL‐9, IL‐10, IL‐13 and IFN‐γ secretion induced from peripheral blood mononuclear cells (PBMC) by a broad panel of inhalant allergens (timothy, cat, birch, dog and house dust mite) in asthmatic children with and without sensitization. The study included 13 atopic asthmatic, 5 non‐atopic asthmatic, and 12 non‐atopic non‐asthmatic children. PBMC were stimulated with allergens and cytokine production was measured with enzyme‐linked immunosorbent assay (ELISA). Higher levels of cat and dog antigen‐induced IL‐5 release were more commonly observed in both atopic and non‐atopic asthmatics than in controls. Children with atopic, but not non‐atopic, asthma produced higher levels of allergen‐induced IL‐4 and IL‐9 than controls. Non‐atopic asthmatics produced more IL‐10 than atopic asthmatics after cat stimulation. High levels of eosinophilia‐associated IL‐5 responses are induced by cat and dog allergen in both atopic and non‐atopic asthmatic children. The Th2 cytokines IL‐4 and IL‐9 were associated only with atopic asthma, probably due to their IgE‐inducing properties.

Summary: Background Immune responses, including those to allergens, may be T helper (Th)2 skewed in newborns. In order to redress the fetal Th1/Th2 imbalance, Th1‐stimulating factors, such as bacterial endotoxin, may be required. The increasing prevalence and severity of atopic diseases in industrialized countries, which are in marked contrast with the low prevalence of allergy among children in the formerly socialist countries of Europe, have been suggested to be caused by a reduced microbial stimulation.Aim To relate the endotoxin levels in house dust from two countries with a low (Estonia) and a high (Sweden) prevalence of allergy to the development of atopic disease and sensitization in the children during the first 2 years of life.Methods The study included 108 children from Tartu, Estonia and 111 children from Linköping, Sweden. Skin prick tests were performed at 3, 6, 12 and 24 months of age, and questionnaires were distributed to the families. At 24 months, a paediatrician examined the children. Dust samples were collected from mattresses and carpets and the endotoxin concentration was determined by a chromogenic Limulus assay.Results The endotoxin levels were higher in Estonian than in Swedish house dust (median levels 29 (range 0.25–280) and 14 (range 0.25–99) EU/mg dust, respectively, P < 0.001). Furthermore, the levels were inversely related to the development of atopic disease and sensitization in the Swedish, but not in the Estonian, children.Conclusions The low prevalence of atopic disease in Estonia may, at least in part, be related to the high endotoxin levels in this country. The findings support that high levels of endotoxin, or other bacterial products with Th1‐stimulating properties, might protect children from developing atopic disease.