Bovine milk fat enriched in conjugated linoleic and vaccenic acids attenuates allergic airway disease in mice

Background It has been argued that a reduction in the Western diet of anti‐inflammatory unsaturated lipids, such as n‐3 polyunsaturated fatty acids, has contributed to the increase in the frequency and severity of allergic diseases. Objective We investigated whether feeding milk fat enriched in conjugated linoleic acid and vaccenic acids (VAs) (‘enriched’ milk fat), produced by supplementing the diet of pasture‐fed cows with fish and sunflower oil, will prevent development of allergic airway responses. Methods C57BL/6 mice were fed a control diet containing soybean oil and diets supplemented with milk lipids. They were sensitized by intraperitoneal injection of ovalbumin (OVA) on days 14 and 28, and challenged intranasally with OVA on day 42. Bronchoalveolar lavage fluid, lung tissues and serum samples were collected 6 days after the intranasal challenge. Results Feeding of enriched milk fat led to marked suppression of airway inflammation as evidenced by reductions in eosinophilia and lymphocytosis in the airways, compared with feeding of normal milk fat and control diet. Enriched milk fat significantly reduced circulating allergen‐specific IgE and IgG1 levels, together with reductions in bronchoalveolar lavage fluid of IL‐5 and CCL11. Treatment significantly inhibited changes in the airway including airway epithelial cell hypertrophy, goblet cell metaplasia and mucus hypersecretion. The two major components of enriched milk fat, cis‐9, trans‐11 conjugated linoleic acid and VA, inhibited airway inflammation when fed together to mice, whereas alone they were not effective. Conclusion Milk fat enriched in conjugated linoleic and VAs suppresses inflammation and changes to the airways in an animal model of allergic airway disease.     

Long-chain polyunsaturated fatty acids are consumed during allergic inflammation and affect T helper type 1 (Th1)- and Th2-mediated hypersensitivity differently

Studies have shown that atopic individuals have decreased serum levels of n‐3 fatty acids. Indicating these compounds may have a protective effect against allergic reaction and/or are consumed during inflammation. This study investigated whether fish (n‐3) or sunflower (n‐6) oil supplementation affected T helper type 1 (Th1)‐ and Th2‐mediated hypersensitivity in the skin and airways, respectively, and whether the fatty acid serum profile changed during the inflammatory response. Mice were fed regular chow, chow + 10% fish oil or chow + 10% sunflower oil. Mice were immunized with ovalbumin (OVA) resolved in Th1 or Th2 adjuvant. For Th1 hypersensitivity, mice were challenged with OVA in the footpad. Footpad swelling, OVA‐induced lymphocyte proliferation and cytokine production in the draining lymph node were evaluated. In the airway hypersensitivity model (Th2), mice were challenged intranasally with OVA and the resulting serum immunoglobulin (Ig)E and eosinophilic lung infiltration were measured. In the Th1 model, OVA‐specific T cells proliferated less and produced less interferon (IFN)‐γ, tumour necrosis factor (TNF) and interleukin (IL)‐6 in fish oil‐fed mice versus controls. Footpad swelling was reduced marginally. In contrast, mice fed fish oil in the Th2 model produced more OVA‐specific IgE and had slightly higher proportions of eosinophils in lung infiltrate. A significant fall in serum levels of long‐chain n‐3 fatty acids accompanied challenge and Th2‐mediated inflammation in Th2 model. Fish oil supplementation affects Th1 and Th2 immune responses conversely; significant consumption of n‐3 fatty acids occurs during Th2‐driven inflammation. The latter observation may explain the association between Th2‐mediated inflammation and low serum levels of n‐3 fatty acids.     

Obesity promotes prolonged ovalbumin‐induced airway inflammation modulating T helper type 1 (Th1), Th2 and Th17 immune responses in BALB/c mice

Clinical and epidemiological studies indicate that obesity affects the development and phenotype of asthma by inducing inflammatory mechanisms in addition to eosinophilic inflammation. The aim of this study was to assess the effect of obesity on allergic airway inflammation and T helper type 2 (Th2) immune responses using an experimental model of asthma in BALB/c mice. Mice fed a high‐fat diet (HFD) for 10 weeks were sensitized and challenged with ovalbumin (OVA), and analyses were performed at 24 and 48 h after the last OVA challenge. Obesity induced an increase of inducible nitric oxide synthase (iNOS)‐expressing macrophages and neutrophils which peaked at 48 h after the last OVA challenge, and was associated with higher levels of interleukin (IL)‐4, IL‐9, IL‐17A, leptin and interferon (IFN)‐γ in the lungs. Higher goblet cell hyperplasia was associated with elevated mast cell influx into the lungs and trachea in the obese allergic mice. In contrast, early eosinophil influx and lower levels of IL‐25, thymic stromal lymphopoietin (TSLP), CCL11 and OVA‐specific immunoglobulin (IgE) were observed in the obese allergic mice in comparison to non‐obese allergic mice. Moreover, obese mice showed higher numbers of mast cells regardless of OVA challenge. These results indicate that obesity affects allergic airway inflammation through mechanisms involving mast cell influx and the release of TSLP and IL‐25, which favoured a delayed immune response with an exacerbated Th1, Th2 and Th17 profile. In this scenario, an intense mixed inflammatory granulocyte influx, classically activated macrophage accumulation and intense mucus production may contribute to a refractory therapeutic response and exacerbate asthma severity.     

UV inhibits allergic airways disease in mice by reducing effector CD4+ T cells

Background In human asthma, and experimental allergic airways disease in mice, antigen‐presenting cells and CD4⁺ effector cells at the airway mucosa orchestrate, and CD4⁺CD25⁺ regulatory T cells attenuate, allergen immunity. UV irradiation of skin before sensitization with ovalbumin (OVA) causes significantly reduced asthma‐like responses in respiratory tissues. Objective To determine whether UV‐induced changes in CD11c⁺ cells, CD4⁺CD25⁺ effector cells or CD4⁺CD25⁺ regulatory cells in the trachea and airway draining lymph nodes (ADLNs) were responsible for reduced allergic airways disease. Methods The phenotype and function of CD11c⁺ cells and CD4⁺CD25⁺ cells in the trachea and ADLNs of UV‐ and non‐irradiated, OVA‐sensitized mice was examined 24 h after a single exposure to aerosolized OVA. Results No changes in the function of CD11c⁺ cells from UV‐irradiated mice were observed. CD4⁺CD25⁺ cells from UV‐irradiated, OVA‐sensitized mice harvested 24 h after OVA aerosol proliferated less in response to OVA in vitro and were unable to suppress the proliferation of OVA‐sensitized responder cells. This result suggested reduced activation of effector T cells in the airway mucosa of UV‐irradiated, OVA‐sensitized mice. To exclude regulatory cells of any type, there was similar proliferation in vivo to aerosolized OVA by CFSE‐loaded, OVA‐TCR‐specific CD4⁺ cells adoptively transferred into UV‐ and non‐irradiated, OVA‐sensitized mice. In addition, there was no difference in the expression of regulatory T cell markers (Foxp3, IL‐10, TGF‐β mRNA). To examine effector T cells, ADLN cells from UV‐irradiated, OVA‐sensitized and ‐challenged mice were cultured with OVA. There was reduced expression of the early activation marker CD69 by CD4⁺CD25⁺ cells, and reduced proliferation in the absence of the regulatory cytokine, IL‐10. Conclusion Reduced allergic airways disease in UV‐irradiated mice is due to fewer effector CD4⁺CD25⁺ cells in the trachea and ADLNs, and not due to UV‐induced regulatory cells. Cite this as: J. P. McGlade, D. H. Strickland, M. J. M. Lambert, S. Gorman, J. A. Thomas, M. A. Judge, J. T. Burchell, G. R. Zosky and P. H. Hart, Clinical & Experimental Allergy, 2010 (40) 772–785.     

Tamoxifen counteracts the allergic immune response and improves allergen‐induced dermatitis in mice

Background Tamoxifen (TX) represents the prototype selective oestrogen receptor modulator. In addition to its use in breast cancer, TX possesses immunomodulatory functions and displays beneficial effects in models of systemic lupus erythematosus. We hypothesized that TX might inhibit type I allergic reactions, which are also characterized by deviations in humoral immunity. Objective To evaluate the effects of TX on the allergic immune response in appropriate mouse models. Methods Balb/c mice were sensitized with ovalbumin (OVA)‐alum by the intraperitoneal route, and humoral parameters, T cell cytokine patterns and OVA‐induced ear swelling responses were determined in a preventive (start of TX treatment before sensitization) and a therapeutic setting (start after sensitization), respectively. In addition, the impact of TX on clinical signs, epidermal thickness and leucocyte infiltration of the skin was investigated in a model of allergen‐induced dermatitis. Results Preventive TX treatment interfered with all aspects of the allergic immune response, leading to a reduction of allergen‐specific Ig levels (IgE, IgG1 and IgG2a), a skewing effect in the T cell compartment with the inhibition of IL‐4 and an abrogation of ear swelling responses. Interestingly, a therapeutic TX administration was also effective in reducing Ig levels and ear swelling responses. The vigorous systemic effects were additionally mirrored by local changes in allergen‐dependent dermatitis with reduced clinical symptoms, diminished epidermal thickness and decreased CD4⁺ and CD8⁺ cell infiltrates. Conclusion TX inhibits allergic responses when given preventively and also therapeutically, and improves allergen‐induced dermatitis. Because of its effectiveness, TX could bear significant therapeutic potential for the treatment of allergies. Cite this as: M. Babina, F. Kirn, D. Hoser, D. Ernst, W. Rohde, T. Zuberbier and M. Worm, Clinical & Experimental Allergy, 2010 (40) 1256–1265.     

Lactation in lean and obese rats: effect of cafeteria feeding and of dietary obesity on milk composition

Changes in milk composition associated with maternal dietary obesity and cafeteria feeding were investigated. Protein, lactose and fat contents, and the fat composition, were determined for lean and obese rats given a cafeteria diet at different stages of reproduction. Feeding the cafeteria diet during lactation resulted in an increase in long-chain fatty acids and a fall in the characteristic medium-chain fatty acids. This effect was modified by obesity and the diet during pregnancy. Feeding the cafeteria diet in lactation reduced the milk protein and increased the fat. The milk of obese rats contained more energy, with more fat but less protein than that of lean rats. Increases in fat and long-chain fatty acid content, and decreases in protein and medium-chain fatty acid content of the milk were correlated with increased maternal intake of energy, total fat and long-chain fatty acids. Thus, the greatest influence on milk composition is exerted by the maternal diet during lactation. However, these effects are modified by pre-existing maternal obesity and the diet during pregnancy.     

Low frequency of filaggrin null mutations in Croatia and their relation with allergic diseases

Filaggrin gene (FLG) null mutations are considered associated with atopic dermatitis. This study was conducted to determine the prevalence of FLG null mutations R501X, 2282del4, R2447X and S3247X in the Croatian population and their role in the occurrence of allergic diseases including atopic dermatitis, allergic rhinitis, asthma and allergic contact dermatitis (ACD). Study enrolled 440 freshmen with defined allergic diseases by means of both present symptoms in International Study of Asthma and Allergies in Childhood questionnaire (relevant respiratory and/or skin symptoms) and markers of allergic sensitization (positive skin prick and/or patch test). FLG null mutations were successfully genotyped in 423 students of which 11 (2.6%) were carriers of FLG null mutation: 1/423 (0.2%) was heterozygous for R501X and 10/423 (2.4%) were heterozygous for 2282del4. No carriers of R2447X and S3247X mutations were identified. In wild‐type FLG carriers (412 subjects), atopic dermatitis was present in 45 (11%), allergic rhinitis in 70 (17%) and allergic asthma in 29 (7%) students. Twenty‐five of 393 (7%) patch‐tested wild‐type FLG carriers had ACD. Among 11 FLG null mutation carriers, four had one or more allergic diseases, and five had reported skin symptoms without defined allergic sensitization (positive skin prick test and/or patch test). FLG null mutations were not confirmed as a predictor of analysed allergic diseases, but were confirmed as an independent predictor of skin symptoms (OR 17.19, 95% CI 3.41–86.6, P < 0.001). Our results in general indicate a low frequency of FLG null mutations in the studied Croatian population supporting a theory of a latitude‐dependent distribution of FGL null mutations in Europe, with a decreasing north–south gradient of R501X and 2282del4 mutation frequency. The relation between FLG null mutations and skin disorders was confirmed.     

Low breast milk levels of long‐chain n‐3 fatty acids in allergic women,despite frequent fish intake

Cite this as: S. Johansson, A. E. Wold and A‐S Sandberg, Clinical & Experimental Allergy, 2011 (41) 505–515.

Summary

Background Long‐chain n‐3 polyunsaturated fatty acids (PUFAs) have immune regulating and anti‐inflammatory effects. However, their role in allergic disease is unclear. Allergic diseases are immunologically heterogeneous, and we hypothesized that n‐3 fatty acid composition in serum and breast milk may vary according to clinical manifestations. Further, animal studies have shown reduction of serum‐PUFA levels during allergic inflammation. Objective To investigate fatty acid composition in breast milk and serum from women with different atopic disease manifestations. Secondly, to determine whether low PUFA levels reflected insufficient intakes. Methods Fatty acids were analysed in breast milk and serum of women with atopic eczema and respiratory allergy (n=16), only respiratory allergy (n=7), as well as healthy women (n=22). Dietary intake of foods expected to affect long‐chain n‐3 PUFA levels were estimated by food‐frequency questionnaire. The fatty acid pattern was related to diagnostic group and intake of relevant food items using a multivariate pattern recognition method (partial least squares projections to latent structures and discriminant analysis). Results Women with a combination of eczema and respiratory allergy had lower breast milk levels of several PUFAs (arachidonic acid, eicosapentaenoic acid, EPA, docosahexaenoic acid, DHA, and docosapentaenoic acid, DPA), and a lower ratio of long‐chain n‐3 PUFAs/n‐6 PUFAs. Their PUFA levels differed not only from that of healthy women, but also from that of women with only respiratory allergy. The latter had a fatty acid pattern similar to that of healthy women. Despite low EPA, DHA and DPA levels women with eczema and respiratory allergy consumed no less fish than did healthy women. Conclusion & Clinical Relevance Our data suggest that reduced levels of long‐chain n‐3 fatty acids in serum and breast milk characterize women with extensive allergic disease including eczema, and are not related to low fish intake. Consumption of PUFAs during the allergic process may explain these findings.     

Gastrointestinal nematode infection interferes with experimental allergic airway inflammation but not atopic dermatitis

Background Some helminth infections are negatively associated with the prevalence of allergic disorders, arguing for a modulation of allergic reactions by the parasites, depending on the worm species, intensity and phase of infection and the type of disease. Objective The aim of this study was to analyse the influence of a chronic infection with the gastrointestinal nematode Heligmosomoides polygyrus, in a murine model of allergic airway disease and of atopic dermatitis (AD), respectively. Methods Mice were infected with H. polygyrus and systemically sensitized with the model allergen ovalbumin. Subsequently, the animals were challenged with the allergen either via the airways for induction of airway disease, or via skin patches for induction of dermatitis. Results Mice concomitantly infected with H. polygyrus showed diminished eosinophil and lymphocyte recruitment into the lungs and decreased allergen‐specific IgE levels when compared with sensitized and airway challenged controls. In addition, animals showed a trend towards reduced airway hyper‐reactivity. In contrast, no significant differences in the severity of eczematous skin lesions were observed between infected and control animals in the AD model. Although H. polygyrus infection reduced CD8⁺ and CD4⁺ T‐cell infiltration into the skin and production of allergen‐specific IgE, mast cell recruitment was significantly increased in worm‐infected mice in the dermatitis model. The worm infection was associated with significantly elevated numbers of Foxp3⁺ regulatory T cells (Treg) in peribronchial lymph nodes in H. polygyrus‐infected sensitized and airway challenged mice. In contrast, Treg cells were basically absent in eczematous skin and their number was not increased in skin‐draining lymph nodes of mice with experimental dermatitis. Conclusion Infection with the gastrointestinal nematode used in our study leads to significant inhibition of mucosa‐associated but not cutaneous allergic reactions, pointing to a site specificity of the immunomodulation exerted by helminths. This finding might be an important aspect for future considerations of helminths for treatment of allergic diseases.     

Effects of different forms of dietary hydrogenated fats on serum lipoprotein cholesterol levels.

BACKGROUND: Metabolic studies suggest that fatty acids containing at least one double bond in the trans configuration, which are found in hydrogenated fat, have a detrimental effect on serum lipoprotein cholesterol levels as compared with unsaturated fatty acids containing double bonds only in the cis configuration. We compared the effects of diets with a broad range of trans fatty acids on serum lipoprotein cholesterol levels. METHODS: Eighteen women and 18 men consumed each of six diets in random order for 35-day periods. The foods were identical in each diet, and each diet provided 30 percent of calories as fat, with two thirds of the fat contributed as soybean oil (<0.5 g of trans fatty acid per 100 g of fat), semiliquid margarine (<0.5 g per 100 g), soft margarine (7.4 g per 100 g), shortening (9.9 g per 100 g), or stick margarine (20.1 g per 100 g). The effects of those diets on serum lipoprotein cholesterol, triglyceride, and apolipoprotein levels were compared with those of a diet enriched with butter, which has a high content of saturated fat. RESULTS: The mean (+/-SD) serum low-density lipoprotein (LDL) cholesterol level was 177+/-32 mg per deciliter (4.58+/-0.85 mmol per liter) and the mean high-density lipoprotein (HDL) cholesterol level was 45+/-10 mg per deciliter (1.2+/-0.26 mmol per liter) after subjects consumed the butter-enriched diet. The LDL cholesterol level was reduced on average by 12 percent, 11 percent, 9 percent, 7 percent, and 5 percent, respectively, after subjects consumed the diets enriched with soybean oil, semiliquid margarine, soft margarine, shortening, and stick margarine; the HDL cholesterol level was reduced by 3 percent, 4 percent, 4 percent, 4 percent, and 6 percent, respectively. Ratios of total cholesterol to HDL cholesterol were lowest after the consumption of the soybean-oil diet and semiliquid-margarine diet and highest after the stick-margarine diet. CONCLUSIONS: Our findings indicate that the consumption of products that are low in trans fatty acids and saturated fat has beneficial effects on serum lipoprotein cholesterol levels.     

Association of breast milk fatty acids with allergic disease outcomes—A systematic review

Introduction

Dietary polyunsaturated fatty acids (PUFAs) have immunoregulatory properties. Breast milk is rich in PUFA, and it has been hypothesized that these PUFAs may be important in the aetiology of allergic diseases. Despite a growing body of evidence, the associations between breast milk PUFA and allergic disease have not previously been systematically reviewed.

Methods

The search was performed in PubMed and EMBASE databases using breastfeeding, fatty acid and allergic disease terms. Two authors were involved in selecting papers for review according to the inclusion criteria and extracting information on study characteristics and measures of association. Only studies that reported numeric associations between concentration of breast milk fatty acids and allergic disease outcomes were included.

Results

A total of 18 papers met the inclusion criteria, reporting results from 15 study populations. The majority were cohort studies (n=11), with data from only two case‐control and two cross‐sectional studies. Sample size varied between 30 and 352 participants, and follow‐up time of the cohorts varied between 3 months and 14 years. Nine studies reported on eczema, seven reported on sensitization, and only five reported on asthma/wheeze. There was heterogeneity among studies in terms of presenting the association between PUFA and allergy; therefore, estimates could not be pooled. Only a few studies observed associations between n‐3 and n‐6 PUFAs and allergic disease, and the magnitude of this effect varied greatly.

Conclusions

There is insufficient evidence to suggest that colostrum or breast milk polyunsaturated fatty acids influence the risk of childhood allergic diseases.     

Infection with the roundworm Toxocara canis leads to exacerbation of experimental allergic airway inflammation

Background Epidemiological studies performed in developing as well as in western countries suggest that infection with Toxocara canis contributes to the development of atopic diseases. Objectives To investigate the association between infection with this helminth and allergy, we examined the effect of T. canis infection on experimental allergic airway inflammation. Methods BALB/c mice were infected by oral administration with 500 embryonated T. canis eggs followed by ovalbumin (OVA) sensitization and challenge to induce allergic airway inflammation. Results Infection with T. canis in combination with OVA treatment leads to exacerbation of pulmonary inflammation, eosinophilia, airway hyperresponsiveness, OVA specific and total IgE. Relative quantification of cytokine expression in the lungs of these mice showed increased expression of IL‐4 compared with mice that were only T. canis infected or OVA treated. Increased expression of IL‐5 and IL‐10 was measured in the lungs of T. canis‐infected or OVA‐treated mice compared with controls; however, combining infection and OVA treatment did not significantly change the expression of these cytokines. Conclusion A previous infection with T. canis leads to exacerbation of experimental allergic airway inflammation. These results have important consequences for findings on the helminths–allergy association. Several factors, including parasite species, infection of definitive vs. accidental host, parasite load and timing of infection, may influence whether an infection with helminths protects one from or enhances allergic manifestations.     

Suppression of the asthmatic phenotype by ultraviolet B-induced, antigen-specific regulatory cells

Background Over recent decades, there has been a significant global increase in the prevalence of asthma, an inflammatory disease of the respiratory system. While ultraviolet radiation (UV) has been used successfully in the treatment of inflammatory conditions such as psoriasis, studies of UV‐induced regulation of allergic respiratory responses have been rare, and have not analysed in vivo measurements of airway hyperresponsiveness (AHR) or the antigen specificity of the UV‐induced effects. Objective To investigate the regulatory properties of erythemal ultraviolet B (UVB) irradiation of the skin and the induction of allergen‐induced airway immunity in a murine asthma model, and to examine the mechanisms involved. Methods BALB/c mice were exposed to a single erythemal dose of UV 3 days before intraperitonial sensitization (day 0) and boost (day 14) with the antigen, ovalbumin (OVA). Airway‐associated, asthma‐like responses to aerosolized OVA at day 21 were analysed including (a) AHR measured in vivo, (b) OVA‐specific proliferative responses and cytokine production by cells from the lung‐draining lymph nodes (LDLN), and (c) inflammatory cells and cytokines in the bronchoalveolar lavage fluid. To determine UVB‐induced mechanisms of regulation, LDLN cells from UVB irradiated, OVA‐sensitized mice were adoptively transferred into naïve BALB/c mice that were subsequently sensitized and challenged with OVA, or a non‐specific antigen. Results UVB irradiation of skin significantly suppressed AHR to methacholine and OVA‐specific responses in the LDLN and in the lung compartment. Reduced OVA‐specific responses by LDLN cells from both UVB irradiated mice and mice that received 5 × 10⁶ LDLN cells from UVB irradiated, but not from non‐irradiated, OVA‐sensitized mice suggested that UVB‐induced regulatory cells are responsible for many of the asthma‐reducing effects of dorsal UVB exposure. Conclusion UVB irradiation of skin suppresses AHR and cellular responses of the airways to respiratory allergens. Further, this study implicates UVB or its downstream mediators as a potential approach to reducing the severity of asthma.     

Polyphenol‐enriched apple extract attenuates food allergy in mice

Background The immune system may be modulated with nutrition to prevent the development or to treat the symptoms of allergy. Among other foods, consumption of apples has been linked to reduced incidence of atopic dermatitis and respiratory allergy. Objective We evaluated the efficacy and mechanisms of a polyphenol‐enriched apple extract in reducing symptoms of food allergy. Methods In a model of food allergy to ovalbumin (OVA), BALB/c mice were fed with an apple extract either during sensitization or just before the challenge. After the challenge, allergic symptoms were scored, OVA‐specific serum immunoglobulins were determined by ELISA, cytokine production by mesenteric lymph node (MLN) cells was measured by a multiplex assay and gene expression profiles in the intestine were addressed using quantitative real‐time PCR. Results Consumption of the apple extract reduced symptoms of food allergy upon challenge. This was paralleled by reduced levels of intestinal mast cell protease, diminished cytokine secretion by MLN cells and reduced local intestinal mRNA expression of various T‐helper type‐2 associated and pro‐inflammatory genes. Mechanistic studies suggested decrease of mediator release by effector cells and reduction of allergenicity by protein–polyphenol interaction as potential mechanisms responsible for protection. Conclusion Polyphenol‐enriched apple extract can attenuate food allergy symptoms in sensitized mice via two distinct possible mechanisms.     

Effect of dietary fat on skin reactivity against histamine, Th1 and Th2 cytokine levels and some serum parameters in mice

Changes in diet may be associated with the increase in allergic disease; change to high-calorie and high-fat diets may be a factor. In this study our objective was to determine skin reactivity of histamine and serum cytokine concentrations in mice fed diets containing different amounts of fat. Histamine reactivity was performed on mice back skin and serum cytokine concentrations were measured by ELISA in mice injected with anti-CD3 antibody. We measured serum interferon-gamma as a Th1-type cytokine and interleukin-4 as a Th2-type cytokine. Mice fed a high fat diet displayed enhanced skin reactivity of histamine and higher IL-4 levels in serum. These data suggest that a high fat diet may play a role in enhancing allergic reactions.     

Polyunsaturated fatty acids in maternal diet, breast milk, and serum lipid fatty acids of infants in relation to atopy

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.     

Increased Th2 activity and diminished skin barrier function cooperate in allergic skin inflammation

Atopic dermatitis (AD) is a chronic inflammatory skin disease induced by a complex interaction between susceptibility genes encoding skin barrier components and environmental allergen exposure that results in type 2 cytokine production. Although genetic lesions in either component can be risk factors for disease in patients, whether these pathways interact in the development of AD is not clear. To test this, we mated mice with T‐cell specific expression of constitutively active Stat6 (Stat6VT) that spontaneously develop allergic skin inflammation with Flaky tail (Ft) mice that have mutations in Flg and Tmem79 genes that each affect skin barrier function. Our results demonstrate that over 90% of the Stat6VT transgenic mice carrying the Ft alleles (Stat6VTxFt^?/?) develop severe atopic dermatitis lesions by 3–5 months of age, compared with only 40% of Stat6VT mice that develop disease by 6–7 months of age. Further, histopathological analysis of skin tissues from Stat6VTxFt^?/? mice revealed extensive thickening of the dermis with increased inflammatory infiltrates as compared with Stat6VT mice. Our study suggests that skin barrier defects and altered Th2 responses independently cooperate in the pathogenesis of allergic skin inflammation, similar to effects observed in patients with AD.     

Basophils as a primary inducer of the T helper type 2 immunity in ovalbumin‐induced allergic airway inflammation

Antigen‐induced allergic airway inflammation is mediated by T helper type 2 (Th2) cells and their cytokines, but the mechanism that initiates the Th2 immunity is not fully understood. Recent studies show that basophils play important roles in initiating Th2 immunity in some inflammatory models. Here we explored the role of basophils in ovalbumin (OVA) ‐induced airway allergic inflammation in BALB/c mice. We found that OVA sensitization and challenge resulted in a significant increase in the amount of basophils in blood and lung, along with the up‐regulation of activation marker of CD200R. However, depletion of basophils with MAR‐1 or Ba103 antibody attenuated airway inflammation, represented by the significantly decreased amount of the Th2 subset in spleen and draining lymph nodes, interlukin‐4 level in lung and OVA‐special immunoglobulin E (sIgE) levels in serum. On the other hand, adoptive transfer of basophils from OVA‐challenged lung tissue to naive BALB/c mice provoked the Th2 immune response. In addition, pulmonary basophils from OVA‐challenged mice were able to uptake DQ‐OVA and express MHC class II molecules and CD40 in vivo, as well as to release interleukin‐4 following stimulation by IgE–antigen complexes and promote Th2 polarization in vitro. These findings demonstrate that basophils may participate in Th2 immune responses in antigen‐induced allergic airway inflammation and that they do so through facilitating antigen presentation and providing interleukin‐4.     

Dietary stearate reduces human breast cancer metastasis burden in athymic nude mice

Stearate is an 18-carbon saturated fatty acid found in many foods in the western diet, including beef and chocolate. Stearate has been shown to have anti-cancer properties during early stages of neoplastic progression. However, previous studies have not investigated the effect of dietary stearate on breast cancer metastasis. In this study, we present evidence that exogenously supplied dietary stearate dramatically reduces the size of tumors that formed from injected human breast cancer cells within the mammary fat pads of athymic nude mice by approximately 50% and partially inhibits breast cancer cell metastasis burden in the lungs in this mouse model system. This metastatic inhibition appears to be independent of primary tumor size, as stearate fed animals that had primary tumors comparable in size to littermates fed either a safflower oil enriched diet or a low fat diet had reduced lung metastasis. Also stearate fed mice sub-groups had different primary tumor sizes but no difference in metastasis. This anti-metastasis effect may be due, at least in part, to the ability of stearate to induce apoptosis in these human breast cancer cells. Overall, this study suggests the possibility of dietary manipulation with selected long-chain saturated fatty acids such as stearate as a potential adjuvant therapeutic strategy for breast cancer patients wishing to maximize the suppression of metastatic disease.