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Notes: Background: The increased consumption of n-6 polyunsaturated fatty acids (PUFA) has been shown to coincide with the increased prevalence of atopic diseases. We aimed to investigate whether maternal diet and atopic status influence the PUFA composition of breast milk and the serum lipid fatty acids of infants. Methods: Maternal diet was assessed by a food questionnaire. The PUFA composition of breast milk obtained at 3 months from 20 allergic and 20 healthy mothers and of their infants' (10 atopic and 10 nonatopic/group of mothers) serum lipids was analyzed. Results: Although no differences in maternal PUFA intake were observed, the breast milk of allergic mothers contained less γ-linolenic acid (18:3 n-6) than that of healthy mothers. Similarly, atopic infants had less γ-linolenic acid in phospholipids than healthy infants, although n-6 PUFA were elevated in other serum lipid fractions in atopic infants. The serum lipid fatty acids in atopic infants did not correlate with those in maternal breast milk. Conclusions: Our results suggest that dietary n-6 PUFA are not as readily transferred into breast milk or incorporated into serum phospholipids, but may be utilized for other purposes, such as eicosanoid precursors, in allergic/atopic individuals. Subsequently, high dietary proportions of n-6 PUFA, or reduced proportions of regulatory PUFA, such as γ-linolenic acid and n-3 PUFA, may be a risk factor for the development of atopic disease.

Notes: Background: The role of dietary fats in food-related allergic symptoms is increasingly being investigated, since the pivotal role of fat-derived inflammatory substances, e.g., leukotrienes, has been realized. The objective of this study was to describe the fatty acid composition of several commercially available infant formulas that are used as substitutes for adapted cow's milk formulas. Methods: Samples of nine formulas (two soy, two extensively hydrolyzed casein, three extensively hydrolyzed whey, and two amino-acid-based formulas) and human milk as control were analyzed by gas chromatography. Results: The quantity of fatty acids in the formulas was within the breast-milk range. The percentage of energy derived from fat was below the European Society for Pediatric Gastroenterology and Nutrition recommendations in two cases, but, in the others, it roughly met the recommendations. The percentage of energy derived from linoleic acid was as recommended in all but two cases, where it was higher than recommended. As indicated by a quality indicator, the linoleic to α-linolenic acid ratio, altogether four formulas were within either the recommendations or the analyzed breast-milk range. In three cases, it was 1.5–2.5 and in two cases 4–5 times higher than recommended. Conclusions: There are recommendations for infant formulas to meet nutritional requirements of fat intake, and the analyzed formulas are in most cases within the suggested ranges. However, little is known of requirements in allergic or inflammatory conditions, and whether these described fatty acid compositions are pro- or anti-inflammatory.

Notes: Current data indicate an obvious relation between food allergy and atopic eczema in infants. However, diagnostic methods for food allergy need to be supplemented. The objective was to study the relevance of food patch testing in the detection of food allergy in correlation with oral food challenge and skin prick tests in atopic infants. Infants with atopic eczema (n = 113) aged 2–24 months were studied. Each patient was subjected to double-blind, placebo-controlled, or open cow's milk challenge, and skin prick and patch tests. Polysensitization, as judged from skin test results, was common in patients with atopic eczema (79/113). Cow's milk challenge was positive in 54/113 infants; reactions were immediate in 36/54 and delayed in 18/54. Immediate-type reactions were associated with skin prick test positivity and delayed reactions with patch test positivity. Altogether 26% of the cow's milk-allergic infants were detected by patch testing only. Patch testing improved the accuracy of skin testing in the diagnosis of food allergy in infants with atopic eczema, but it needs to be standardized. Polysensitization appears to be more common than generally believed among infants with atopic eczema.

Notes: A prerequisite for systemic hyporesponsiveness to dietary antigens is their processing in the gut. This study investigated whether bovine caseins degraded by enzymes of an intestinal bacterial strain, Lactobacillus GG (ATCC 53103), could regulate the cytokine production by anti-CD3 antibody-induced peripheral blood mononuclear cells of 14 atopic patients, aged 5–29 (mean, 16) months. Purified casein up-regulated the interleukin-4 and interferon-γ production, P = 0.008 and P = 0.008, respectively. Conversely, Lactobacillus GG-degraded casein down-regulated the interleukin-4 production, P = 0.003, with no effect on interferon-γ. These results indicate that intestinal bacteria may modify immunomodulatory properties of native food proteins and introduce a promising tool to provide protection from potentially harmful dietary antigens at a young age.

Notes: Previous studies have shown that in cow milk allergy the specific immune response to dietary cow milk antigens is deficient. This study aimed at delineating the development of humoral immune response to cow milk antigens in healthy infants. Twenty-five healthy newborns were enrolled, and seen at scheduled visits at the ages of three, six and eleven months, and they formed two groups: those breastfed and those fed adapted cow milk formulae. The local immune response in the gut was approximated using the ELISPOT assay of circulating antibody secreting cells. At the age of three months, in the formula fed group, cells secreting specific IgA to cow milk antigens were detected despite low levels of IgA serum antibodies. The total number of IgA secreting cells increased with age (p = 0.001). The milk in the infant diet directly influenced this development so that the age related increase was significantly greater in the formula fed group (p = 0.04). The results indicate that diet has a significant effect on the developing immune system, and that healthy infants are able to respond in an antigen specific fashion to dietary antigens, which may be central in attaining clinical tolerance of such antigens.

Notes: To assist in identifying pathogenetic mechanisms in different clinical manifestations of cow's milk allergy (CMA), the involvement of eosinophil cells in immunoinflammatory reactions was evaluated. The study population comprised 28 patients, aged from 5.8 to 43.0 months, who had challenge-proven CMA, manifested either cutaneously (n = 17) or gastrointestinally (n = 11). A clinical cow's milk challenge was performed in hospital after a 4 week cow's milk elimination period. Eosinophil activation in vivo was studied by measuring the serum level of eosinophil cationic protein (ECP) before the oral cow's milk challenge, mean (SD) 27 (12) hours after commencing the challenge and one week later. These results were compared to those of 80 non-allergic age-matched controls. During the challenge, the level of ECP increased from 6.2 (4.5, 8.0) μg/L to 20.0 (9.5, 30, 4) μg/L in CMA patients with skin manifestations but not in those with gastrointestinal symptoms. The increase was shown to be transient. We conclude that eosinophil degranulation is an important immunologic mechanism leading to allergic inflammation in cutaneously manifested CMA.

Notes: The cellular immune response to cow's milk was measured in patients with challenge-proven cow's milk allergy (CMA), manifested with either gastrointestinal or skin symptoms. After 2–4 weeks on milk elimination, 44 children, mean (SD) age 15.7 (9.4) months, were challenged, and cow's milk-induced lymphocyte transformation was measured before the clinical challenge (Day 1) and / or one week later (Day 8). During the clinical challenge period, 17 (39%) patients showed gastrointestinal reactions, 9 (20%) had urticarial or eczematous skin eruptions, and 18 (41%) were negative to challenge. On Day 1, the mean [95% confidence interval] stimulation index for lymphocytes in patients manifesting CMA with gastrointestinal symptoms, 2.60 [1.60, 4.10], was significantly higher than that in patients with skin symptoms, 1.15 [0.60, 2.30], or patients with negative clinical challenge, 0.83 [0.64, 1.08], F = 9.0, p = 0.001. After the clinical challenge (Day 8), this cow's milk-induced lymphocyte proliferation response was abrogated. At the same time, CMA patients evidenced a significantly higher spontaneous lymphocyte proliferation response in RPMI medium-containing control cultures than those with negative clinical challenge. We conclude that in patients with CMA, the number of circulating cow's milk-sensitized lymphocytes is depleted or their function is impaired after clinical exposure to cow's milk antigens.

Notes: To assist in identifying pathogenetic mechanisms in different subtypes of cow's milk allergy (CMA), the function of immunoregulatory T-lymphocytes was studied. The study population consisted of 23 patients, mean [95% confidence interval] age of 25. 6 [19. 5, 33. 6] months, who had challenge-proven cow's milk allergy manifested with either skin (n=9) or gastrointestinal (n=14) symptoms; in addition, 13 age-matched disease controls were studied. Patients with challenge-proven CMA were rechallenged to establish whether they had acquired clinical tolerance to cow's milk. The suppressor activity of isolated lymphocytes was measured in vitro by a cell coculture at rechallenge and in 10/23 patients at diagnosis. At diagnosis, patients with CMA (n=10) showed a decreased mean [95% CI] suppressor activity, induced by either Concanavalin A, 7[-2, 15]%, or cow's milk, 3[-8, 14]% as compared with disease controls (n = 13), 19[15, 24]% and 24[17, 31]%; F = 7. 1, p = 0.004 and F = 6. 7, p = 0.005, respectively. At rechallenge the suppressor activity, induced both by Concanavalin A and cow's milk, reached the level of disease controls only in patients who had acquired clinical tolerance to cow's milk (n = 13/23), but not in those retaining CMA (n = 10/23). Our results indicate that the maturation of suppressor function is delayed in CMA, which might be of primary importance in the etiopathogenesis of CMA.

Notes: We have investigated the role of interferon-gamma (IFN-gamma) in the regulation of antigen-specific T-cell function in patients with cow's milk allergy. The study population consisted of 22 patients, aged from 7. 6 to 56. 9 months, who had challenge-proven cow's milk allergy (CMA) manifested with either skin (n=9) or gastrointestinal (n=13) symptoms. In addition, 11 age-matched children and 6 adults, mean (SD) age 31 (7) years, were studied as controls. Patients with challenge-proven CMA were rechallenged to establish whether they had acquired clinical tolerance to cow's milk. The spontaneous and mitogen-induced IFN-gamma and interleukin-4 (IL-4) generation of isolated lymphocytes was evaluated in vitro with commercial ELISA Kits at diagnosis and at reassessment. At diagnosis, the IFN-gamma production was not detectable in patients with CMA as compared with control children. IL-4 production was almost undetectable in all subjects in this study. However, at reassessment the CMA patients who had acquired clinical tolerance to cow's milk (n=16) showed enhanced IFN-gamma production, when compared with that of control children, but still lower when compared with that of healthy adults. Our results indicate that the maturation of IFN-gamma producing T-cells is delayed in CMA, which could lead to a disturbance in the regulation of T-cell function. This defect might be an important etiologic factor for CMA.

Notes: Over the last two decades the incidence of allergic diseases has increased in industrialized countries, and consequently new approaches have to be explored.〈section xml:id="abs1-2"〉〈title type="main"〉ObjectiveThe potential of probiotics to control allergic inflammation at an early age was assessed in a randomized double-blind placebo-controlled study.〈section xml:id="abs1-3"〉〈title type="main"〉MethodsA total of 27 infants, mean age 4.6 months, who manifested atopic eczema during exclusive breast-feeding and who have had no exposure to any infant or substitute formula were weaned to probiotic-supplemented, Bifidobacterium lactis Bb-12 or Lactobacillus strain GG (ATCC 53103), extensively hydrolysed whey formulas or to the same formula without probiotics. The extent and severity of atopic eczema, the growth and nutrition of infants, and concentrations of circulating cytokines/chemokines and soluble cell surface adhesion molecules in serum and methyl-histamine and eosinophilic protein X in urine were determined.〈section xml:id="abs1-4"〉〈title type="main"〉ResultsThe SCORAD score reflecting the extent and severity of atopic eczema was 16 (7–25) during breast-feeding, median (interquartile range). After 2 months, a significant improvement in skin condition occurred in patients given probiotic-supplemented formulas, as compared to the unsupplemented group; χ2 = 12.27, P = 0.002. SCORAD decreased in the Bifidobacterium lactis Bb-12 group to 0 (0–3.8), and in the Lactobacillus GG group to 1 (0.1–8.7), vs unsupplemented 13.4 (4.5–18.2), median (interquartile range), in parallel with a reduction in the concentration of soluble CD4 in serum and eosinophilic protein X in urine.〈section xml:id="abs1-5"〉〈title type="main"〉ConclusionThe results provide the first clinical demonstration of specific probiotic strains modifying the changes related to allergic inflammation. The data further indicate that probiotics may counteract inflammatory responses beyond the intestinal milieu. The combined effects of these probiotic strains will guide infants through the weaning period, when sensitization to newly encountered antigens is initiated. The probiotic approach may thus offer a new direction in the search for future foods for allergy treatment and prevention strategies.